Ca2+ is widely recognized as an essential intracellular second messenger in eukaryotic systems regulating processes such as muscle contraction, neurotransmitter release, gene expression and cell proliferation. The effects of Ca2+ are frequently mediated via interaction with calmodulin (CaM) and strong evidence indicates, in turn, that the effects of Ca2+/CaM are often achieved through the regulation of protein phosphorylation. A family of CaM-dependent protein kinases has been identified that includes: myosin light chain kinase, phosphorylase kinase, CaM kinase I, CaM kinase II, EF-2 kinase (CaM kinase III) and CaM kinase IV. The structure, regulation and function of this important family of second messenger-regulated protein kinases will be briefly reviewed.