The co-inhibitory receptor programmed death-1 acts to dampen immune responses in peripheral tissues via interaction with its widely distributed ligand(s). The latter function as a final 'shield' to protect tissues from immunological attack by T cells and help to maintain peripheral tolerance and prevent autoimmunity. Upregulation in a variety of cancers is thought to be one mechanism by which they evade immunological eradication. The study by Topalian and colleagues evaluating the role of blockade of this pathway with a monoclonal antibody in patients with advanced cancer is reviewed. This large Phase I study demonstrates encouraging response rates in patients with melanoma, renal cell carcinoma and non-small-cell lung cancer. Although the spectrum of toxicity was similar to that seen with blockade of cytotoxic T-lymphocyte antigen 4, the severity appeared lower in most cases. After a long wait, it finally seems that immune-based anticancer therapies are emerging to become part of the mainstream.