Cell‐cycle control is a major determinant of homeostasis during B‐cell development, differentiation, and tumorigenesis. The generation of an antibody response requires activation and expansion of antigen‐specific B cells and terminal differentiation of these cells into plasma cells. Plasma cells arrest in the G1 phase of the cell cycle, but the mechanism that underlies timely cell‐cycle entry and exit in the humoral immune response is not known. The mammalian cell‐cycle is regulated primarily at the G1 to S transition by the balance between positive regulators, the cyclin‐dependent kinases (CDK) together with cyclins, and negative regulators, the CDK inhibitors. One such inhibitor, p18^INK4c, has been shown to be required for cell‐cycle termination and final differentiation of non‐secreting plasmacytoid cells to antibody‐secreting plasma cells. This finding provides the first direct evidence for cell‐cycle control of B‐cell immunity. It also raises important questions regarding cell‐cycle control of cellular differentiation, apoptosis, and earlier steps of B‐cell terminal differentiation. This article discusses the biochemical mechanism of cell‐cycle control in the context of antibody response and plasma cell differentiation along with the role of cell‐cycle dysregulation in the pathogenesis of multiple myeloma, the plasma cell cancer.