Antibodies are an essential component of our immune system, underpinning the effectiveness of both the primary immune response to microbial pathogens and the protective and long‐lived immunity against re‐challenge. All antibodies are produced by relatively rare populations of plasmablasts and plasma cells, collectively termed antibody‐secreting cells (ASCs). It is now apparent that ASCs are unique in the body in terms of their gene expression program and metabolic pathways that enable these cells to have an extraordinary rate of immunoglobulin gene transcription, translation, assembly and secretion. In this review we will discuss the cellular, metabolic and molecular specialization that allows ASCs to maintain such high rates of antibody production, in some cases for the life of the individual. Throughout the review we will link these exquisite cellular and molecular adaptations to the major regulators of ASC gene expression, in an attempt to define how the ASC phenotype and function is genetically programmed.