This review is focused on the cellular dynamics and genomic programming of plasma cell (PC) precursors that arise during germinal center (GC) B cell responses in secondary lymphoid organs (SLOs) and give rise to PCs in the bone marrow. Considerable progress has been made in the phenotypic characterization of circulating and bone marrow PC precursors as well as their differentiated short‐lived (SLPC) and long‐lived (LLPC) counterparts, in the context of model antigen and vaccine responses. Importantly, it has been possible to infer the temporal dynamics of generation of PC precursors during a GC response. However, the nature of the PC precursors at their site of generation in SLOs, and their signaling and genomic states, remain to be elucidated. Our synthesis draws upon experimental studies conducted in murine models as well as in humans, the latter complemented with cell culture manipulations of PCs and their precursors. By integration of the studies in murine and human systems, which are being accelerated by new genomic methodologies, we highlight insights and hypotheses concerning the generation of PCs. This framework can be extended and explored from both fundamental and translational standpoints.