Inducing cross-reactive broadly neutralizing antibody (bNAb) responses to HIV through vaccination remains an insurmountable challenge. T follicular helper (T_FH) cells are fundamental for the development of antigen-specific antibody responses and therefore crucial for anti-HIV vaccine design. Here, we review recent studies supporting an intricate involvement of T_FH cells in HIV pathogenesis and bNAb development during HIV infection. We also examine emerging data suggesting that T_FH cell responses may be traceable in peripheral blood, and discuss the implications of these findings in the context of vaccine design and future research in T_FH cell immunobiology.