T helper 22 (Th22) cells, a newly defined CD4+ T-cell lineage, are characterized by their distinct cytokine profile, which primarily consists of IL-13, IL-22 and TNF-α. Th22 cells express a wide spectrum of chemokine receptors, such as CCR4, CCR6 and CCR10. The main effector molecule secreted by Th22 cells is IL-22, a member of the IL-10 family, which acts by binding to IL-22R and triggering a complex downstream signaling system. Th22 cells and IL-22 have been found to play variable roles in human immunity. In preventing the progression of infections such as HIV and influenza, Th22/IL-22 exhibited protective anti-inflammatory characteristics, and their deleterious proinflammatory activities have been demonstrated to exacerbate other illnesses, including hepatitis B and Helicobacter pylori infection. Herein, we review the current understanding of Th22 cells, including their definition, differentiation and mechanisms, and the effect of Th22/IL-22 on human infectious diseases. According to studies on Th22 cells, Th22/IL-22 may be a promising therapeutic target and an effective treatment strategy for various infections.