Calcium is a signaling element of general importance to cells. In muscle, its key function is the activation of troponin C, which is essential for the contraction of myofibrils in skeletal and heart muscles, and of myosin light chain kinase, which is essential for the contraction of smooth muscles. Calcium modulates the latter enzyme through the calcium-binding protein calmodulin, which may also control other calcium-binding proteins involved in the contraction of smooth muscles. The control of calcium within cells requires the reversible and specific complexation by proteins that are either soluble in the cytoplasm (e.g., calmodulin), intrinsic to membranes (e.g., ATPases, Ca exchangers), or organized in nonmembranous structures (e.g., troponin C). Two Ca pumps (i.e., ATPases) are responsible for a large portion of the Ca movements across membrane barriers. One is located in sarco(endo)plasmic reticulum; in muscles, it moves back and forth the Ca2+ that is directly involved in the activation of the myofibrils. The other is located in the plasma membrane. Together with a Na/Ca exchanger that is also located there, it maintains the large Ca gradient normally existing between cells and extracellular spaces.