Immune-regulatory mechanisms are used by cancer to hide from the immune system. 
Advances and in-depth understanding of the biology of melanoma and its 
interaction with the immune system have led to the development of some of 
antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its 
ligands, programmed death ligand 1 (PD-L1), which are demonstrating high 
clinical benefit rates and tolerability. Blocking the immune-regulatory 
checkpoints that limit T-cell responses to melanoma upon PD-1/PD-L1 modulation 
has provided clinically validated targets for cancer immunotherapy. Combinations 
with other anti-melanoma agents may result in additional benefits. Nivolumab, 
pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are 
anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung 
cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other 
cancers. Long-term survivors already have been reported with these therapies. In 
this review, we discuss the current state of anti-PD-1 agents, the evidence in 
the literature to support the combination of anti-PD-1 antibodies with other 
anti-cancer agents and discuss the future directions for rational design of 
clinical trials that keep on increasing the number of long-term survivors.