Cells and tissues can be seen, from the perspective of Materials Science and Engineering, as “smart materials and structures”. In fact, cells and tissues are able to perceive and respond to several environmental stimuli and gradients of them, including the presence of biochemical cues and microorganisms, the mechanical and topographical properties of the extra cellular matrix and surfaces upon which they lie, the application of vibrations and the surrounding electromagnetic fields, to cite just a few, as already detailed in several chapters of the Handbook. Advances in technologies for manipulating, culturing and monitoring single cells, together with progress in the fields of modeling, simulation, prototyping and testing, have led to a better understanding of how cells respond to several types of stimuli and accurate predictions about the behavior of cells and tissues are already possible. In consequence, cells and tissues can be employed as living transducers for the development of (micro-)sensors and (micro-)actuators, as it is possible to predict and control their responses. This chapter provides and introduction to the development of cell-based sensors and actuators and to current main challenges in this novel area. Once such challenges are solved, the frontiers between biological systems, machines and synthetic engineering systems in general will start to fade away. An approach for a more rapid solution of the aforementioned challenges, towards a wide-spread use of cell-based sensors and actuators, may rely on the use of systematic libraries with CAD models of conceptual cell-based sensors and actuators, both for modeling and prototyping strategies, as proposed in a final case study included in present chapter.