This chapter provides an overview of the sensing mechanisms and transducers utilized in various types of CMOS biosensors, which are critical for detecting and measuring biological signals and chemical reactions. It offers a comprehensive exploration of various sensing mechanisms central to CMOS microelectrode systems and related technologies, including voltammetric, impedimetric, capacitive, optical, magnetic, and temperature sensors. The chapter details the electrode-electrolyte system, CMOS microelectrode structures, and fabrication, and explores microelectrode arrays (MEAs) for neural applications. It also examines Biological/Chemical Field-Effect Transistors (Bio/ChemFETs), their physics, operational regions, and fabrication, followed by a discussion on optical and magnetic sensing mechanisms. Additionally, it covers Nuclear Magnetic Resonance (NMR) principles and various temperature sensing methods, providing a deep understanding of their roles in different sensing environments.