Adrenocorticotrophic hormone (ACTH) is derived from the prohormone, pro-opiomelanocortin (POMC). This precursor undergoes proteolytic cleavage to yield a number of different peptides which vary depending on the tissue. In the anterior pituitary, POMC is processed to ACTH by the prohormone convertase, PC1 and packaged in secretory granules ready for stimulated secretion. In response to stress, corticotrophin releasing hormone (CRH), stimulates release of ACTH from the pituitary cell which in turn causes release of glucocorticoids from the adrenal gland. In tissues, such as the hypothalamus and skin, ACTH is further processed intracellularly to alpha melanocyte stimulating hormone (alphaMSH) which has distinct roles in these tissues. The prohormone, POMC, is itself released from cells and found in the human circulation at concentrations greater than ACTH. While much is known about the tightly regulated synthesis of POMC, there is still a lot to learn about the mechanisms for differentiating secretion of POMC, and the POMC-derived peptides. Understanding what happens to the POMC released from cells will provide new insights into its function.