The article reviews the role of regulatory B cells (Bregs) in various human diseases and their potential as prognostic and therapeutic targets. Bregs are a diverse group of B lymphocytes that suppress inflammatory immune responses, contributing to immune homeostasis and tolerance. Key molecules involved in Breg function include IL-10, IL-35, TGF-β, and granzyme B. Bregs play a crucial role in reducing pathological inflammatory reactions associated with transplant rejection, graft-versus-host disease, autoimmune diseases, allergies, infections, neoplasms, and metabolic disorders. The review highlights the diverse phenotypic and transcriptional properties of Bregs, which can be induced by various factors such as cytokines, B cell receptors, and Toll-like receptors. Despite their potential, there are currently no clinical approaches to modulate Breg activity, and the translation of Breg-based therapies into clinical practice remains challenging due to species differences. The authors suggest that GMP-compliant manufacturing processes for autologous or HLA-matched allogeneic Bregs may offer a promising direction for future research and clinical applications.The article reviews the role of regulatory B cells (Bregs) in various human diseases and their potential as prognostic and therapeutic targets. Bregs are a diverse group of B lymphocytes that suppress inflammatory immune responses, contributing to immune homeostasis and tolerance. Key molecules involved in Breg function include IL-10, IL-35, TGF-β, and granzyme B. Bregs play a crucial role in reducing pathological inflammatory reactions associated with transplant rejection, graft-versus-host disease, autoimmune diseases, allergies, infections, neoplasms, and metabolic disorders. The review highlights the diverse phenotypic and transcriptional properties of Bregs, which can be induced by various factors such as cytokines, B cell receptors, and Toll-like receptors. Despite their potential, there are currently no clinical approaches to modulate Breg activity, and the translation of Breg-based therapies into clinical practice remains challenging due to species differences. The authors suggest that GMP-compliant manufacturing processes for autologous or HLA-matched allogeneic Bregs may offer a promising direction for future research and clinical applications.