Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play critical roles in inducing and controlling B cell responses, including the generation of high-affinity humoral immunity, the antibody class-switching, and the prevention of autoreactivity. Successful Tfh responses are linked to robust vaccine-induced neutralizing antibody production and efficient clearance of various pathogens. Conversely, dysregulation of follicular T cells is often linked to autoimmune diseases and allergic reactions. Furthermore, these cells are implicated in the formation of ectopic lymphoid structures (ELS), contribute to certain vascular pathologies, and hold prognostic value in several cancers. Consequently, the analysis of follicular T cell subpopulations in human peripheral blood is increasingly utilized to investigate the mechanisms underlying various diseases. In this opinion article, the current understanding of follicular T cell subsets, their functions, and the evolving methods for analyzing their circulating counterparts in human blood are discussed. In the author's opinion, the central unresolved questions remaining in the field are the precise phenotypic definition of circulating Tfr cell subpopulations, the elucidation of their developmental trajectory from precursors cells to mature regulatory forms, and the identification of their anatomical differentiation niches. The collection and translation of these essential data into reliable cellular signatures for peripheral blood analysis are critical for advancing personalized patient prognosis and developing tailored therapies.