Melanocortins appear to be involved as regulators in an ever growing number of physiological processes in cells and tissues of diverse functions. While such trends are apparent also in the case of other peptide hormones, it appears that melanocortin receptors can be regarded as unique among G-protein-linked receptors due to their special need for extracellular Ca2+ which may relate to some, yet undetermined selectivity of their actions. The physiological role that Ca2+ may be playing and the diverse signaling mechanisms regulated, as well as the nature of the cell-specific responses elicited in melanocortin-sensitive cells/tissues, have yet to be elucidated. Likewise, it will be of interest to establish the relationship of melanocortins to processes like growth and differentiation of cells, as well as to higher, more complex processes such as those regulated in the CNS.