Contractions of skeletal muscles provide the stability and power for all body movements. Consequently, any impairment in skeletal muscle function results in some degree of instability or immobility. Factors that influence skeletal muscle structure and function are therefore of great interest scientifically and clinically. Injury, neuromuscular disease, and old age are among the factors that commonly contribute to impairments in skeletal muscle function. The goal of this chapter is to summarize the fundamentals of skeletal muscle structure and function to provide foundational knowledge for this Handbook volume. We examine the molecular interactions that provide the basis for the generation of force and movement, discuss mechanisms of the regulation of contraction at the level of myofibers, and introduce concepts of the activation and control of muscle function in vivo. Where appropriate, the chapter updates the emerging science that will increase understanding of muscle function.