•Immune checkpoint blockade inhibitors are revolutionizing the care for patients with cancer.•Specifically, anti-PD-1 and anti-PD-L1 agents have demonstrated marked clinical success in a wide range of malignancies by providing durable benefits with minimal toxicities.•Herein, we review the pre-clinical and clinical activity of these agents in multiple malignancies.•In addition, we review areas that need further development in order to improve the clinical efficacy of these agents. Immunotherapy for the treatment of cancer is rapidly evolving from therapies that globally and non-specifically simulate the immune system to more targeted activation of individual components of the immune system. The net result of this targeted approach is decreased toxicity and increased efficacy of immunotherapy. More specifically, therapies that inhibit the interaction between programmed death ligand 1 (PD-L1), present on the surface of tumor or antigen-presenting cells, and programmed death 1 (PD-1), present on the surface of activated lymphocytes, are generating much excitement and enthusiasm, even in malignancies that are not traditionally considered to be immunogenic. Herein, we review the current landscape of anti-PD-1 and anti-PD-L1 therapies in the world of oncology. We have performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, the ClinicalTrials.gov registry, and abstracts from major oncology meetings in order to summarize the clinical data of anti-PD-1/PD-L1 therapies.