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Systems and methods of use for continuous analyte measurement of a host's vascular system are provided. In some embodiments, a continuous glucose measurement system includes a vascular access device, a sensor and sensor electronics, the system being configured for insertion into communication with a

Systems and methods of use for continuous analyte measurement of a host's vascular system are provided. In some embodiments, a continuous glucose measurement system includes a vascular access device, a sensor and sensor electronics, the system being configured for insertion into communication with a host's circulatory system.

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1. A continuous analyte detection system, comprising: a continuous analyte sensor configured for contact with a sample from a circulatory system of a host and configured to generate a first signal and a second signal, wherein the first signal is a measurement of a glucose oxidase catalyzed reaction

1. A continuous analyte detection system, comprising: a continuous analyte sensor configured for contact with a sample from a circulatory system of a host and configured to generate a first signal and a second signal, wherein the first signal is a measurement of a glucose oxidase catalyzed reaction product with glucose and the second signal is a measurement of a reference analyte; a reference sensor configured to generate a reference signal that is a measurement of the reference analyte; anda processor module configured to process the second signal and the reference signal to calibrate the first signal. 2. The system of claim 1, wherein the continuous analyte sensor comprises a first working electrode and a second working electrode, wherein the first working electrode is disposed beneath an active glucose oxidase portion of a sensor membrane and is configured to generate a signal that is a measurement of glucose and non-glucose related electroactive compounds, wherein the non-glucose related electroactive compounds have an oxidation potential that substantially overlaps with an oxidation potential of the glucose oxidase catalyzed reaction product with glucose; wherein the second working electrode is disposed beneath an inactive-enzymatic or a non-enzymatic portion of the sensor membrane and is configured to generate a signal that is a measurement of the related non-glucose related electroactive species, and wherein the processor module is configured to process signals from the first working electrode and second working electrode, whereby the first signal is generated substantially without a non-glucose-related signal component. 3. The system of claim 2, wherein the first working electrode is further configured to generate the second signal. 4. The system of claim 2, wherein the second working electrode is further configured to generate the second signal. 5. The system of claim 1, wherein the reference sensor comprises an optical sensing apparatus. 6. The system of claim 1, wherein the reference sensor is disposed in a same local environment as the continuous analyte sensor. 7. The system of claim 1, further comprising a flow control device configured to meter a flow of a fluid. 8. A continuous analyte detection system, comprising: a continuous analyte sensor configured for contact with a sample from a circulatory system of a host and configured to generate a first signal and a second signal,wherein the first signal is a measurement of a test analyte and the second signal is a measurement of a reference analyte;wherein the continuous analyte sensor comprises a first working electrode, a second working electrode, and a third working electrode, wherein the first working electrode is disposed beneath an active enzymatic portion of a sensor membrane and is configured to generate a signal corresponding to glucose and non-glucose related electroactive compounds, wherein the non-glucose related electroactive compounds have an oxidation potential that substantially overlaps with an oxidation potential of a glucose oxidase catalyzed reaction product with the glucose test analyte; wherein the second working electrode is disposed beneath an inactive-enzymatic or a non-enzymatic portion of the sensor membrane and is configured to generate a signal corresponding to the non-glucose related electroactive species, wherein the third working electrode is disposed beneath the sensor membrane and configured to generate the second signal, and wherein the processor module is configured to process signals from the first working electrode and second working electrode, whereby the first signal is generated substantially without a non-glucose-related signal component;a reference sensor configured to generate a reference signal corresponding to the reference analyte; anda processor module configured to process the second signal and the reference signal to calibrate the first signal. 9. A continuous analyte detection system, comprising: a continuous analyte sensor configured for contact with a sample from a circulatory system of a host, wherein the continuous analyte sensor comprises a working electrode configured to generate both a first signal and a second signal, wherein the first signal is a measurement of a glucose oxidase catalyzed reaction product with glucose and the second signal is a measurement of a reference analyte;a reference sensor configured to generate a reference signal corresponding to the reference analyte; anda processor module configured to process the second signal and the reference signal to calibrate the first signal. 10. A continuous analyte detection system, comprising: an analyte sensor comprising a membrane system, wherein the analyte sensor is configured to generate a measurement signal that is a measurement of a glucose oxidase catalyzed reaction product with glucose in vivo, and wherein the analyte sensor is further configured to generate a reference signal that is a measurement of a reference analyte concentration in vivo;reference sensor located proximal to the analyte sensor and configured to generate a reference value that is a measurement of the reference analyte, wherein the reference sensor is located proximal to the analyte sensor; anda processor module configured to process the reference signal and the reference value to calibrate the measurement signal. 11. The system of claim 10, wherein the processor module is configured to calibrate the measurement signal without an external reference value. 12. The system of claim 10, wherein the system is configured for automatic calibration of the measurement signal. 13. The system of claim 10, wherein the system is configured such that the analyte sensor and the reference sensor are located within the same local environment such that the reference concentration measured by the analyte sensor and the reference concentration measured by the reference sensor are substantially equal. 14. The system of claim 10, wherein the analyte sensor is an electrochemical sensor and the reference sensor is an optical sensor.