Humoral immunity depends on the regulated production and maintenance of antibody secreting cells during the course of an immune response. Recent insights into the transcriptional regulation of the initiation of plasma cell differentiation have clarified aspects of this process, particularly with respect to the choice between the memory B cell and plasma cell differentiation pathways. It is now possible to specify the conditions favouring these outcomes and to predict where they might occur within the germinal center. Once formed, plasma cell survival is critically dependent on accessing niches that are formed by stomal elements in both normal and inflamed tissues. The apparent homeostasis of plasma cell numbers means that new specificities can persist only at the expense of existing ones, raising questions on how immunological memory is maintained in the face of new immune responses. The answer appears to be through the reduction of the process to a single cell level, thereby introducing an element of stochasticity.