Follicular regulatory T (TFR) cells are a population of CD4+ T-cells that concomitantly express markers for regulatory T-cells and follicular helper T (TFH) cells, and have been predominantly implicated in the regulation of humoral immunity via their suppressive functions. Rapid and robust progress has been made in the field of TFR cell research since the discovery of this subset over a decade ago. However, there is still a significant gap in our understanding of the mechanisms underlying the phenotypic and functional heterogeneity of TFR cells under various physiologic and pathologic settings. In this review article, we aim to highlight the most up-to-date concepts and investigations in both experimental animal models and human studies to provide a perspective on our understanding of TFR biology with particular emphasis on these cells in the context of disease settings.