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Immune checkpoint molecules are crucial in controlling immune responses. One of these molecules is the programmed cell death protein 1 (PD-1), which limits T-cell effector functions against chronic inflammation and cancer by binding to its primary ligand, PD-L1. When PD-1 binds to its ligand, PD-L1, the ability of the activated T cell to produce an effective immune response is down modulated. Antibodies directed against PD-1 or the PD-1 ligand may restore or augment an antitumor immune response and produce tumor responses in patients with advanced melanoma. The ability of anti-PD-1 inhibitors to induce durable tumor responses and the elevated therapeutic index has promoted studies with these drugs either as monotherapy or in different combinations, including those with other novel immunotherapy agents, in patients with advanced disease. Herein we review the pharmacological properties, the activity, efficacy and toxicity of pembrolizumab and summarize new potential therapeutic strategies, which could potential expand its spectrum of activity in melanoma.