Abstract Immunotherapy has recently emerged as the fourth pillar of cancer treatment, joining surgery, radiation, and chemotherapy. While early immunotherapies focused on accelerating T-cell activity, current immune-checkpoint inhibitors take the brakes off the anti-tumor immune responses. Successful clinical trials with PD-1 monoclonal antibodies and other immune-checkpoint inhibitors have opened new avenues in cancer immunology. However, the failure of a large subset of cancer patients to respond to these new immunotherapies has led to intensified research on combination therapies and predictive biomarkers. Here we summarize the development of PD-1-blockade immunotherapy and current issues in its clinical use.