Adaptive immunity plays an important role in the host defense of pathogens, among which CD4+ T helper cell takes a major part. The regulation of Th cell differentiation, the function they exerts in immune response, autoimmune diseases, and allergic conditions, has long attracted much attention. Naive CD4+ T cells differentiate into distinct subsets after receiving TCR and costimulation signaling for activation and cytokine signaling to direct their differentiation. In this chapter, we will have a broad overview of all Th cell subsets, including Th1, Th2, Th17, Treg, Tfh, as well as Th9 and Th22.