This chapter provides a comprehensive overview of the adverse effects associated with immune checkpoint inhibitor (ICI) therapy in cancer treatment. It begins by introducing the concept of immune-related adverse events (irAEs) as a consequence of boosting antitumor immune responses. It then systematically explores irAEs affecting various organ systems, including the skin, endocrine glands, eyes, joints, nervous system, gastrointestinal tract, lungs, heart, liver, kidneys, and hematological system. For each organ system, the chapter discusses the incidence, clinical presentation, underlying mechanisms, diagnostic approaches, and management strategies for specific irAEs. A wide range of irAEs from common manifestations such as skin rashes and thyroid dysfunction to rarer but potentially life-threatening complications such as myocarditis and pneumonitis are covered. The chapter emphasizes the importance of early recognition and appropriate management of these adverse events to ensure the safe and effective use of ICIs in cancer therapy. It also highlights the variability in irAE occurrence based on the type of ICI used and the potential for combination therapies to increase the risk and severity of adverse events. Throughout the chapter, insights into the immunological mechanisms underlying irAEs, the role of various immune cells and cytokines, and the potential overlap between irAEs and autoimmune disorders are provided. The chapter also explains on the use of biomarkers to predict and monitor irAEs, as well as the challenges in managing these complications while maintaining the antitumor efficacy of ICI therapy.