Proopiomelanocortin (POMC) is a polypeptide hormone precursor that is expressed in the brain and in peripheral tissues such as in the pituitary gland, immune system, and skin. In the brain, POMC is processed to form several peptides including alpha-melanocyte stimulating hormone (α-MSH). alpha-MSH is expressed in the hypothalamic arcuate nucleus and in the nucleus tractus solitarius of the brainstem where it has a crucial role in the regulation of metabolic functions. Specifically, α-MSH is an anorexigenic peptide. Its production and maturation processes have been shown to be regulated according to the metabolic condition of the organism. This review summarizes our current knowledge on α-MSH processing including its maturation and degradation processes and pharmacological aspects of its manipulation.