Secondary metabolism is not only a protective mechanism against biotic and abiotic stresses but also part of the molecular programs that contribute to normal plant growth and development. In this context, secondary metabolism is intimately linked with other aspects of plant differentiation in which transcription factors play a key coordinating role. Recent findings illustrate the complexity of regulatory networks that control flavonoid biosynthesis in Arabidopsis and other species. They also underline the close relationship between secondary metabolism and epidermal and seed differentiation in Arabidopsis, and the central role played by conserved WD40 domain proteins in regulating these processes. This review highlights recent advances in this field and describes how they help our understanding of the molecular regulation of plant secondary metabolism.