Preventing or curing an immune-mediated disease requires functional immune cells, in particular T cells, including helper (CD4+; Th) and cytotoxic (CD8+; Tc) T cells. Based on the type of the antigen presenting cells, the nature of antigens, and the cytokine milieu, CD4+ T cells exhibit high plasticity to differentiate into different subsets with stimulatory or regulatory functions. For instance, Th cells can differentiate into Th1 and Th2 type cells, which produce inflammatory (IL-2, IFN-γ, TNF-α, IL-12) and anti-inflammatory (IL-4, IL-10, and TGF-ß) cytokines, respectively. Th cells can also differentiate into a third type of Th cells designated as Th17 type cell that produces IL-17 and mimics the effects of Th1 cells. Similar to Th cells, Tc can differentiate into Tc1, Tc2, and Tc17 subsets that produce cytokine profiles similar to those produced by Th1, Th2, and Th17 cells, respectively. Under certain condition, Th type cells can also differentiate into a regulatory (Treg) type cell, which produces immunosuppressive cytokines such as TGF-ß and IL-10. Similarly, Th17 and Tc1 type cells can acquire immunoreglatory properties. This article sheds a light on how this T cell plasticity shapes the nature of the immune cell responses to inflammation, infection, and cancer.