Significant advances in the genetic and molecular characterization of cancer have led to the development of effective immunotherapies. These therapeutics help the host immune system recognize cancer as foreign, promote the immune system, and relieve the inhibition that allows growth and spread of tumors. Experience with various immunotherapies, particularly the immunomodulatory monoclonal antibody ipilimumab, has demonstrated that unique patterns of response may be encountered that cannot be adequately captured by traditional response criteria, such as the World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), which have been used primarily with cytotoxic chemotherapies. In response to these observations, several novel response criteria have been developed to evaluate patients who receive immunotherapy, including immune-related response criteria (irRC), immune-related RECIST (irRECIST), and immune RECIST (iRECIST). These criteria are typically used in conjunction with RECIST version 1.1 in the clinical trial setting, because approval of new therapeutics by the US Food and Drug Administration relies on the responses derived from RECIST version 1.1. Finally, a wide variety of immune-related adverse events may affect patients who receive immunotherapy, many of which can be identified on imaging studies such as computed tomography, magnetic resonance imaging, and 2-deoxy-2-(fluorine-18)fluoro-D-glucose-positron emission tomography/computed tomography. In this review, the authors present the role of imaging in the evaluation of patients treated with immunotherapy, including the background and application of irRC, irRECIST, and iRECIST; the imaging of immune-related adverse events; and future directions in advanced imaging of immunotherapy. Cancer 2018;124:2906-22. © 2018 American Cancer Society.