Follicular helper T cells (Tfh) are a newly defined helper T-cell subset that is specialized in facilitating B-cell responses. These cells have a unique tissue localization pattern and a distinct transcriptional program suited for the B-cell helper function. Co-opting of the follicular program affords regulatory T cells, NK T cells, and γδ T cells with opportunities to participate in the regulation of humoral immunity. Abnormal Tfh development and function can lead to immunodeficiencies, autoimmune inflammation, and tumors. Detailed understanding of Tfh cell differentiation and function in animal models and the human system promises better strategies toward vaccine development and therapies for inflammatory diseases.