The locomotor activity of laboratory mice is a global behavioral trait which can be valuable for the primary phenotyping of genetically engineered mouse models as well as mouse models of pathologies affecting the central and peripheral nervous systems, the musculoskeletal system, and the control of energy homeostasis. Basal levels of mouse locomotion can be recorded using infrared monitoring of movements, and further information can be gathered by giving the animal access to a running wheel, which will greatly enhance its spontaneous physical activity. Described here are two detailed protocols to evaluate basal locomotor activity and spontaneous wheel running. Curr. Protoc. Mouse Biol. 1:185-198. © 2011 by John Wiley & Sons, Inc.