Cation channels play a major role in fast and sustained cellular responses to hormones and neurotransmitters. They contribute to depolarization of the membrane and--in most cases--to an increase in the intracellular Ca2+ concentration. Nonselective cation channels presumably form a large family of diverse channels which are modulated by various extracellular and intracellular signals. Structure and regulation of ligand-operated and cyclic nucleotide-activated nonselective cation channels found in synapses and sensory receptor cells, respectively, are well documented; none of the structures of other cation channels are known. Except for ligand-operated and stretch-activated channels, G-proteins form the link between the involved receptors and signalling cascades stimulating nonselective cation channels. Observed in numerous cellular systems is hormonal activation of cation channels by hormones or neurotransmitters interacting with heptahelical receptors inducing a phosphoinositide breakdown (PI response); several pathways stimulated within the PI response may generate signals involved in cation channel activation. Pharmacological modifications of nonselective cation channels by inorganic and organic blockers are so far extremely limited; various blockers have been described but unfortunately lack high specificity for these channels.