Th cell functional subsets have unique transcriptional programs that form the molecular basis for T cell differentiation and functions. T follicular helper (T FH) cells have emerged as the main providers of T cell help to B cells during the germinal center (GC) reaction, where B cells undergo selection events through competition for Ag and for access to GC T cell-mediated prosurvival and differentiation signals. Because T cell help is one limiting factor for GC B cells, the molecular mechanisms controlling T FH cell abundance and functionality are central to the GC reaction and generation of long-term humoral immunity. Two signaling pathways are absolutely critical for T FH cells: phosphoinositide-3 kinase pathway and the signaling lymphocyte activation molecule-associated protein. In this review, the molecular mechanisms constituting the signaling network in T FH cells will be explored.