SummaryInterleukin‐22 (IL‐22) has important functions in host defense at mucosal surfaces as well as in tissue repair. It is unique as a cytokine that is produced by immune cells, including T‐helper (Th) cell subsets and innate lymphocytes, but acts only on non‐hematopoietic stromal cells, in particular epithelial cells, keratinocytes, and hepatocytes. Although IL‐22 is beneficial to the host in many infectious and inflammatory disorders, depending on the target tissue it can be pathogenic due to its inherent pro‐inflammatory properties, which are further enhanced when IL‐22 is released together with other pro‐inflammatory cytokines, in particular IL‐17. To avoid pathology, IL‐22 and IL‐17 production have to be controlled tightly and independently. While common factors such as signal transducer and activator of transcription 3 (STAT3) and retinoid orphan receptor γt (RORγt) drive the expression of both cytokines, other factors, such as c‐Maf act specifically on IL‐22 and enable the separate expression of either cytokine. Here, we discuss the production of IL‐22 from various T‐cell populations as well as protective versus pathogenic roles of IL‐22. Finally, we focus on recent advances in our understanding of the molecular regulation of IL‐22 in T cells.