Since the development and approval of Ipilimumab, the first immune checkpoint inhibitor licensed for the treatment of metastatic melanoma, clinicians have gained a better understanding of the mode of action, management of toxicities, and assessment of response to this class of drugs. Several antibodies are now in development, aimed at blocking novel immune checkpoint molecules, such as PD-1 and it's corresponding ligand PD-L1. This article summarizes the mechanism of action, preclinical development, and subsequent clinical studies of immune checkpoint antibodies in melanoma.