Insulin stimulates glucose uptake in striated muscle and fat via a complex cascade of signaling events. Insulin resistance in these tissues and type 2 diabetes constitute major and rapidly increasing health problems in society. Recent research implicates an important role of Ca2+ in insulin-mediated glucose uptake. Maneuvers that increase or decrease Ca2+ influx also increase or decrease insulin-mediated glucose uptake both in normal and insulin-resistant cells. Ca2+ appears to act on late steps in the insulin-signaling cascade, that is, the docking and fusion of glucose transporter 4 (GLUT4) vesicles with the plasma membrane. No Ca2+ sensor in this process has yet been explicitly identified but recent studies point at synaptotagmin VII and the motor protein Myo1c as possible candidates.