Follicular helper T (T_FH) cells are essential for B-cell maturation and immunoglobulin production after immunization with thymus-dependent antigens. Nevertheless, the development and function of T_FH cells have been less clearly defined than classic CD4⁺ effector T-cell subsets, including T-helper-1 (T_H1), T_H2 and T_H17 cells. As such, our understanding of the genesis of T_FH cells in humans and their role in the development of autoimmunity remains incomplete. However, evidence from animal models of systemic lupus erythematosus (SLE) and patients with systemic autoimmune diseases suggests that these cells are necessary for pathogenic autoantibody production, in a manner analogous to their role in promotion of B-cell maturation during normal immune responses. In this Review, I discuss the findings that have increased our knowledge of T_FH-cell development and function in normal and aberrant immune responses. Such information might improve our understanding of autoimmune diseases, such as SLE, and highlights the potential of T_FH cells as therapeutic targets in these diseases.