Nature Reviews Drug Discovery, Published online: 24 July 2026; doi:10.1038/s41573-026-01495-3 T follicular helper (TFH) cells support B cell function to promote long-lasting antibody responses but are implicated in many diseases and undergo age-related changes. This Review explores emerging therapeutic strategies to modulate TFH cells, including boosting their function for vaccination and infectious disease or limiting it in autoimmune disease, cancer and allergy.