Transient receptor potential (TRP) cation channels represent a large and diverse family of ion channels that act as important transducers of sensory information. The Melastatin subfamily member TRPM7 has garnered much interest due to its functional kinase domain; a unique feature among ion channels. TRPM7 primarily conducts Ca(2+) and Mg(2+) and its activity is regulated by intracellular Mg(2+), phospholipase C-mediated signaling and mechanical cues. A growing number of studies emphasize a regulatory role for TRPM7 in proliferation and cell survival as well as cytoskeletal reorganization during adhesion and migration. Knockout approaches in animal models have revealed that TRPM7 significantly contributes to embryonic development and organogenesis. In addition, a role for TRPM7 to the pathophysiology of several diseases has become evident in recent years. Here, we discuss how recent insights have contributed to our understanding of TRPM7 function and regulation in health and disease.