Immune check point inhibitor (CPI) therapy has revolutionized treatment paradigms for several cancers, but at the cost of triggering a diverse spectrum of immune-mediated injury to non-cancer tissues. The complex biology of these toxicities remains incompletely understood, partly because tissue acquisition from affected areas can be challenging to retrieve, thus hindering development of targeted therapy. Here, we review the literature describing pathology of immune-mediated tissue lesions including gastrointestinal, skin, rheumatic, pulmonary, cardiac, renal and hepatic lesions and highlight key immunological insights.