Tumors have developed multiple immunosuppressive mechanisms to turn down the innate and the effector arms of the immune system, thus compromising most of the immunotherapeutic strategies that have been proposed during the last decade. Right after the pioneering success of Ipilimumab (anti-CTLA4) in metastatic melanoma, several groups have conducted trials aiming at subverting other immune checkpoints. Two articles that recently appeared in the New England Journal of Medicine.(1) (,) (2) highlight the therapeutic potential of agents that target PD-1 or its ligand PD-L1 in patients with advanced cancer, even individuals with lung or brain metastases. If confirmed, this clinical breakthrough will open novel avenues for cancer immunotherapy.