The introduction of immune checkpoint inhibitors (ICI) has rapidly changed the treatment and prognosis of numerous tumor entities. In general, therapy with ICI is better tolerated than conventional chemotherapy, but also displays a novel spectrum of side effects due to its mechanism of action. The blocking of immune checkpoints can result in increased or even excessive immune responses. These immune-related adverse events (irAE) can involve almost all organ systems, although skin, intestinal tract, endocrine system, lungs and liver are most commonly affected. Timely diagnosis of irAE is crucial and usually classified according to Common Terminology Criteria for Adverse Events criteria. In the context of PD-1/PD-L1 (PD-1: programmed death protein 1, PD-L1: programmed cell death 1 ligand 1) monotherapy, immune-associated adverse events are usually mild to moderate; grade 3/4 toxicities occur only with a frequency of about 14%. Dual checkpoint blockade (CTLA-4 [cytotoxic T‑lymphocyte-associated protein 4]+ PD-1/PD-L1) is significantly more toxic and shows grade 3/4 adverse events in the range of 30–50%. However, severe or even life-threatening toxicities are rare. At the onset of grade ≥3 toxicity, an immediate stop of ICI therapy is mandatory. Initially, the management of the irAE consists of topical or systemic steroid administration, an escalation of therapy with additional immunosuppressants depends on severity and organ involvement as well as on response to steroids.