The control of gene expression is critical to the proper development of all organisms. Genetic control at the posttranslational level is an important system of such regulation. Recent developments in the understanding of the proteases involved in the endoproteolytic cleavage of prohormones to produce active hormones have begun to provide insight into the tissue-and developmental-specific events of posttranslational processing. This review will discuss the development of our understanding of the action and regulation of these proteases, including KEX2, furin and the prohormone-converting enzymes, PC1 and PC2.