Follicular dendritic cells (FDCs) are unique accessory immune cells that contribute to the regulation of humoral immunity. They are multitasker cells essential for the organization and maintenance of the lymphoid architecture, induction of germinal center reaction, production of B memory cells, and protection from autoimmune disorders. They perform their activities through both antigen-driven and chemical signaling to B cells. FDCs play a crucial role in the physiological regulation of the immune response. Dis-regulation of this immune response results when FDCs retain antigens for years. This provides a constant antigenic stimulation for B cells resulting in the development of immune disorders. Antigen trapped on FDCs is resistant to therapeutic intervention causing chronicity and recurrences. Beyond their physiological immunoregulatory functions, FDCs are involved in the pathogenesis of several immune-related disorders including HIV/AIDS, prion diseases, chronic inflammatory, and autoimmune disorders. FDCs have also been recently implicated in rare neoplasms of lymphoid and hematopoietic tissues. Understanding FDC biology is essential for better control of humoral immunity and opens the gate for therapeutic management of FDC-mediated immune disorders. Thus, the biology of FDCs has become a hot research area in the last couple of decades. In this review, we aim to provide a comprehensive overview of FDCs and their role in physiological and pathological conditions.