Biological systems respond to and communicate through biophysical cues, such as electrical, thermal, mechanical and topographical signals. However, precise tools for introducing localized physical stimuli and/or for sensing biological responses to biophysical signals with high spatiotemporal resolution are limited. Inorganic semiconductors display many relevant electrical and optical properties, and they can be fabricated into a broad spectrum of electronic and photonic devices. Inorganic semiconductor devices enable the formation of functional interfaces with biological material, ranging from proteins to whole organs. In this Review, we discuss fundamental semiconductor physics and operation principles, with a focus on their behaviour in physiological conditions, and highlight the advantages of inorganic semiconductors for the establishment of biointerfaces. We examine semiconductor device design and synthesis and discuss typical signal transduction mechanisms at bioelectronic and biophotonic interfaces for electronic and optoelectronic sensing, optoelectronic and photothermal stimulation and photoluminescent in vivo imaging of cells and tissues. Finally, we evaluate cytotoxicity and highlight possible new material components and biological targets of inorganic semiconductor devices.