In recent years, increasing knowledge about in vitro cell handling and culturing has encouraged a variety of CMOS-based approaches to stimulate and detect electrical activity of biological cells. This paper outlines in a topical review the scope of cell-based biosensors and actuators for in vitro applications ranging from single-cell detection to multisite probing of complex neural tissue. Recent examples are selected to demonstrate how standard CMOS processes have been used to engineer arrays with different functionality.