Calcium has a major role in regulating epidermal functions, including cell proliferation, terminal differentiation, and cell-to-cell adhesion. Aberrations in calcium regulation have been noted in psoriasis when levels of the calcium binding protein calmodulin are elevated, and the normal calcium gradient within the epidermis is altered. Calcium may also be important in neoplasia because similar elevations in calmodulin have been noted in transformed cells. The function of calcium in mediating cell-cell adhesion may be important in understanding the acantholysis observed in pemphigus. The pemphigus foliaceus antigen appears to contain a calcium-sensitive epitope, and in pemphigus vulgaris, alteration in the function of calcium-sensitive cadherins may play a role in the production of acantholysis. Further understanding of the function of calcium in these processes may, in the future, allow us to alter calcium metabolism as a therapeutic intervention.