Plasma cells are cellular factories devoted entirely to the manufacture and export of a single product: soluble immunoglobulin (Ig). As the final mediators of a humoral response, plasma cells play a critical role in adaptive immunity. Although intense effort has been devoted to studying the regulation and requirements for early B cell development, little information has been available on plasma cells. However, more recent work—including studies on genetically altered mice and data from microarray analyses—has begun to identify the regulatory cascades that initiate and maintain the plasma cell phenotype. This review will summarize our current understanding of the molecules that regulate commitment to a plasma cell fate and those that mediate plasma cell function.