This chapter provides a comprehensive overview of cancer immunotherapy using immune checkpoint blockade. It begins by introducing the concept of tumor immune surveillance and how tumors evade the immune response. The chapter then explains the development and current state of immune checkpoint inhibitors (ICIs) in cancer treatment. It covers FDA-approved ICIs targeting CTLA-4, PD-1, PD-L1, and LAG-3, as well as emerging ICIs targeting molecules such as TIM-3, TIGIT, and B7-H3. The chapter discusses the mechanisms of action, clinical efficacy, and approved indications for various ICIs. It also explores combination therapy approaches, including the use of multiple ICIs together or ICIs with other cancer treatments such as chemotherapy, radiation, and targeted therapies. The chapter addresses the challenges of ICI therapy, including limited response rates and the need for predictive biomarkers. It examines FDA-approved biomarkers such as PD-L1 expression, tumor mutational burden, and microsatellite instability, as well as emerging biomarkers such as tumor-infiltrating lymphocytes and gene signatures. Finally, the chapter discusses factors that can influence ICI efficacy, including the gut microbiome and diet, highlighting potential strategies to enhance treatment outcomes.