Immune checkpoint inhibitors are a new class of cancer therapeutics that have demonstrated striking successes in a rapid series of clinical trials. Consequently, these drugs have dramatically increased in clinical use since being first approved for advanced melanoma in 2011. Current indications in addition to melanoma are non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, and classical Hodgkin lymphoma. A small subset of patients treated with immune checkpoint inhibitors undergoes an atypical treatment response pattern termed pseudoprogression: New or enlarging lesions appear after initiation of therapy, thereby mimicking tumor progression, followed by an eventual decrease in total tumor burden. Traditional response standards applied at the time of initial increase in tumor burden can falsely designate this as treatment failure and could lead to inappropriate termination of therapy. Currently, when new or enlarging lesions are observed with immune checkpoint inhibitors, only follow-up imaging can help distinguish patients with pseudoprogression from the large majority in whom this observation represents true treatment failure. Furthermore, the unique mechanism of immune checkpoint inhibitors can cause a distinct set of adverse events related to autoimmunity, which can be severe or life threatening. Given the central role of imaging in cancer care, radiologists must be knowledgeable about immune checkpoint inhibitors to correctly assess treatment response and expeditiously diagnose treatment-related complications. The authors review the molecular mechanisms and clinical applications of immune checkpoint inhibitors, the current strategy to distinguish pseudoprogression from progression, and the imaging appearances of common immune-related adverse events. ©RSNA, 2017.