Toxoplasma gondii infection is an important cause of central nervous system and ocular disease, both in immunocompromised and in certain immunocompetent populations. Although parasite-mediated host cell lysis is probably the principal cause of tissue destruction in immunodeficiency states, hypersensitivity and inflammatory responses may underlie severe disease in otherwise immuno-sufficient individuals. In this review, we have critically evaluated the body of experimental evidence indicating a role of CD4 T cells in systemic and local immunopathology associated with T. gondii infection. We also discuss the pathogenic roles of cytokines produced by T helper (Th) 1 and Th17 cells and the protective and homeostatic roles of interleukin (IL)-10, transforming growth factor-beta and IL-27 in modulating hypersensitivity responses induced by T. gondii.