This paper deals with instrumenting a mechatronic system, through the incorporation of suitable sensors, actuators, and other required hardware. Sensors (e.g., semiconductor strain gauges, tachometers, RTD temperature sensors, cameras, piezoelectric accelerometers) are needed to measure (sense) unknown signals and parameters of a system and its environment. The information acquired in this manner is useful in operating or controlling the system, and also in process monitoring; experimental modeling (i.e., model identification); product testing and qualification; product quality assessment; fault prediction, detection and diagnosis; warning generation; surveillance, and so on. Actuators (e.g., stepper motors, solenoids, dc motors, hydraulic rams, pumps, heaters/coolers) are needed to “drive” a plant. Control actuators (e.g., control valves) perform control actions, and in particular they drive control devices. Micro-electromechanical systems (MEMS) use microminiature sensors and actuators. MEMS sensors commonly use piezoelectric, capacitive, electromagnetic and piezoresistive principles. MEMS devices provide the benefits of small size and light weight (negligible loading errors), high speed (high bandwidth), and convenient mass-production (low cost). The process of instrumentation involves the identification of proper sensors, actuators, controllers, and signal modification/interface hardware, and software with respect to their functions, operation, parameters, ratings, and interaction with each other, so as to achieve the performance requirements of the overall system, and interfacing/integration/tuning of the selected devices into the system, for a given application. This paper presents the key steps of instrumenting a mechatronic system, in a somewhat general and systematic manner. Examples are described to illustrate several key procedures of instrumentation.