This article will present a review of our recent work on the development of Complementary Metal-Oxide Semiconductor (CMOS) detection and signal processing interfaces for fluorescence based biochemical sensors as well as the development of a new sensor. We will discuss a number of microsystems that integrate CMOS Application Specific Integrated Circuits (ASICs) with nanoporous sensor materials. Specifically, sol-gel derived xerogel thin films, a class of nanoporous materials, are employed for monitoring various biochemical analytes including oxygen (O2), glucose, and pH. We have also demonstrated a single-chip CMOS based phase fluorometric system for monitoring O2 using xerogel sensor materials. In this paper, we will present a new, versatile, CMOS based platform for real-time phase fluorometric analysis that is capable of functioning with fluorophores having excited-state lifetimes as short as 400 nanoseconds. In addition, we will describe the employment of novel nanomaterials (porous polymer photonic bandgap structures) as immobilization media for biochemical recognition elements that enhance the fluorescence detection efficiency. Finally, the development of integrated sensors using these materials will be described.