Ca2+-activated Cl channels (CaCCs) perform many important functions in cell physiology including secretion of fluids from acinar cells of secretory glands, amplification of olfactory transduction, regulation of cardiac and neuronal excitability, mediation of the fast block to polyspermy in amphibian oocytes, and regulation of vascular tone. Although a number of proteins have been proposed to be responsible for CaCC currents, the anoctamin family (ANO, also known as TMEM16) exhibits characteristics most similar to those expected for the classical CaCC. Interestingly, this family of proteins has previously attracted the interest of both developmental and cancer biologists. Some members of this family are up-regulated in a number of tumours and functional deficiency in others is linked to developmental defects.