The blockade of immune checkpoints is a promising approach to activating therapeutic antitumour immunity. Immune checkpoints are inhibitory pathways that regulate the immune response to maintain self-tolerance and modulate the duration and amplitude of physiological immune responses. Tumours often co-opt these pathways to resist immune attack, particularly against T cells specific for tumour antigens. Antibodies or recombinant ligands/receptors can block these checkpoints, enhancing antitumour immunity. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) was the first checkpoint inhibitor to achieve FDA approval, followed by programmed cell death protein 1 (PD1). Clinical trials with PD1 blockers show broad and diverse opportunities to enhance antitumour immunity, with potential for durable clinical responses. The biology of CTLA4 and PD1 pathways, their clinical applications, and the development of biomarkers to predict responses are discussed. The diverse set of antigens expressed by cancers provides a basis for the development of multiple immune checkpoint targets, with ongoing clinical trials evaluating their efficacy and safety.The blockade of immune checkpoints is a promising approach to activating therapeutic antitumour immunity. Immune checkpoints are inhibitory pathways that regulate the immune response to maintain self-tolerance and modulate the duration and amplitude of physiological immune responses. Tumours often co-opt these pathways to resist immune attack, particularly against T cells specific for tumour antigens. Antibodies or recombinant ligands/receptors can block these checkpoints, enhancing antitumour immunity. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) was the first checkpoint inhibitor to achieve FDA approval, followed by programmed cell death protein 1 (PD1). Clinical trials with PD1 blockers show broad and diverse opportunities to enhance antitumour immunity, with potential for durable clinical responses. The biology of CTLA4 and PD1 pathways, their clinical applications, and the development of biomarkers to predict responses are discussed. The diverse set of antigens expressed by cancers provides a basis for the development of multiple immune checkpoint targets, with ongoing clinical trials evaluating their efficacy and safety.