In recent years, T follicular helper (Tfh) cells have emerged as the key cell type required for the formation of GCs and the generation of long-lived serological memory. Similar to other CD4+ T cell lineages (Th1, Th2, Th17, and regulatory T [T reg] cells), the generation of Tfh cells requires signaling pathways activated downstream of cytokines and cell surface molecules, and the subsequent activation of specific transcription factors. Here, we discuss recent advances in understanding the requirements for the generation and acquisition of effector function by Tfh cells.