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Unlike a controlled in vitro test environment, the in vivo environment immediately at the surface of a sensor is in a constant state of change due to short-term influences (activity level, inflammation, diet, temperature swings, sun exposure, and other stressors) and long-term influences. However, sensor designers need to have an intimate understanding of the biological environment in which their sensor will reside. Approaches to develop better implantable sensors have been largely engineering based, with often minor input from biologists, physiologists, immunologists, pathologists, and other disciplines with biological expertise. Many clever attempts have been made to develop long-term, continuous glucose sensors, which can function exceptionally well on the benchtop (i.e., in vitro) but often perform unreliably once implanted into the body (i.e., in vivo). The symposium is published in two parts part I was published in the September 2010 issue ( ), and part II is published in this May 2011 issue ( ). This special symposium titled “Interstitial Fluid Physiology as It Relates to Glucose Monitoring Technologies” is intended to help to bridge the gap in our understanding. However, ISF physiology as it relates to glucose sensors is not well understood. Nearly all commercially available glucose sensors share the subcutaneous (SQ) interstitial fluid (ISF) compartment as their preferred implantation site.