The transcriptional regulatory mechanisms that control gene expression during differentiation and contractile protein accumulation are becoming well understood in skeletal and cardiac muscle lineages. Current understanding of smooth muscle–specific gene transcription is much more limited, though recent studies have begun to shed light on this topic. In this review, we summarize some of the themes emerging from these studies and identify transcriptional regulatory elements common to several smooth muscle genes. These include potential binding sites for serum response factor, Sp1, AP2, Mhox, and YY1, as well as a potential transforming growth factor-β control element. We speculate that it may be possible to manipulate smooth muscle–specific gene expression in asthma or pulmonary arterial hypertension as an eventual therapy. Solway J, Forsythe SM, Halayko AJ, Vieira JE, Hershenson MB, Camoretti-Mercado B. Transcriptional regulation of smooth muscle contractile apparatus expression.