Cancer immunotherapies have remarkably changed therapy approaches in many types of cancers. In contrast to traditional cytotoxic cancer treatments, immunotherapy can promote the immune system to clear cancer cells and induce atypical response patterns such as “pseudoprogression,” characterized by expansion of the primary tumor followed by tumor shrinkage. Although relatively infrequent, atypical responses have significant importance for patient surveillance. The World Health Organization (WHO) criteria were published in 1981 to standardize the assessment of solid tumors’ response to systemic therapies. The RECIST 1.0 Criteria, proposed in 2000, established specific guidelines to assess tumor response defining the minimum lesion size and the total number of measurable lesions. WHO and RECIST do not accurately estimate immune response patterns. New response protocols have been developed to assess neoplastic tissue’s physiological and functional characteristics after immunotherapy: irRC (immune-related) in 2009, irRECIST in 2013, and iRECIST(immune) in 2017. Other new criteria are mRECIS (modified), used in the assessment of hepatocellular carcinoma, and CHOI criteria for gastrointestinal stromal tumors (GIST). In the era of immuno-oncology, radiologists play a crucial role in interpreting imaging results and communicating with clinicians to ensure patients receive the appropriate treatment. This chapter aims to describe imaging assessment response, traditional and new criteria assessment, immune-related adverse events, and possible future directions.