The article reviews the CTLA-4 and PD-1 pathways, which are negative regulators of T-cell immune function. Inhibition of these pathways has led to the development of new immunotherapies for various cancers, including melanoma and non-small cell lung cancer. Ipilimumab, an inhibitor of CTLA-4, is approved for advanced melanoma, while nivolumab and pembrolizumab, PD-1 inhibitors, are approved for advanced melanoma and metastatic non-small cell lung cancer. The roles of CTLA-4 and PD-1 in inhibiting immune responses, particularly antitumor responses, are distinct. CTLA-4 regulates T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in the response, mainly in peripheral tissues. The clinical profiles of immuno-oncology agents targeting these checkpoints may vary based on their mechanistic differences. The article provides an overview of the CTLA-4 and PD-1 pathways and discusses the implications of their inhibition in cancer therapy.The article reviews the CTLA-4 and PD-1 pathways, which are negative regulators of T-cell immune function. Inhibition of these pathways has led to the development of new immunotherapies for various cancers, including melanoma and non-small cell lung cancer. Ipilimumab, an inhibitor of CTLA-4, is approved for advanced melanoma, while nivolumab and pembrolizumab, PD-1 inhibitors, are approved for advanced melanoma and metastatic non-small cell lung cancer. The roles of CTLA-4 and PD-1 in inhibiting immune responses, particularly antitumor responses, are distinct. CTLA-4 regulates T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in the response, mainly in peripheral tissues. The clinical profiles of immuno-oncology agents targeting these checkpoints may vary based on their mechanistic differences. The article provides an overview of the CTLA-4 and PD-1 pathways and discusses the implications of their inhibition in cancer therapy.