IL‐22 is a Th17 T‐cell‐associated cytokine that is highly expressed during chronic inflammation. IL‐22 receptor expression is absent on immune cells, but is instead restricted to the tissues, providing signaling directionality from the immune system to the tissues. Through Stat3 signaling, IL‐22 induces a variety of proliferative, anti‐apoptotic, and anti‐microbial pathways. IL‐22 is bi‐functional with both pro‐inflammatory and protective effects on tissues depending on the inflammatory context. The cytokine plays a role both in the host response against extracellular pathogens and in the inflammation associated with autoimmune diseases. Therapeutics targeting IL‐22 therefore may have promise for treating various chronic inflammatory diseases.