Proteoglycans are among the most complex and sophisticated molecules of mammalian systems in terms of their protein and carbohydrate moieties. These macromolecules are in a continuous interplay with each other and the cell surface signal-transducing pathways, some of which are beginning to be elucidated. Because of their domain structure, catalytic potential, and diversity, these molecules appear to be designed for integrating numerous signaling events. For example, some proteoglycans interact with hyaluronan and lectins, thereby linking cell surfaces and distant matrix molecules. Some interact with collagen during the complex process of fibrillogenesis and regulate this biological process fundamental to animal life. Others interact with growth factors and serve as depot available during growth or tissue remodeling. In this review, we center on the most recent developments of proteoglycan biology, focusing primarily on genomic organization and transcriptional and posttranscriptional control. We discuss only those proteoglycans whose gene and promoter elements have been characterized and proved to be functional. When possible, we correlate the effects of growth factors and cytokines on proteoglycan gene expression with the topology of cis-acting elements in their genomic control regions. The analysis leads to a comprehensive critical appraisal of the principles that underlie the regulation of proteoglycan gene expression and to the delineation of common regulatory mechanisms.