Morphological, functional, molecular and cell biology studies have revealed a striking multifunctional nature of individual smooth muscle cells (SMC). SMCs manifest phenotypic plasticity in response to changes in environment and functional requirements, acquiring a range of structural and functional properties bounded by two extremes, called "synthetic" and "contractile." Each phenotypic state is characterized by expression of a unique set of structural, contractile, and receptor proteins and isoforms that correlate with differing patterns of gene expression. Recent studies have identified signaling pathways and transcription factors (e.g., RhoA GTPase/ROCK, also known as Rho kinase, and serum response factor) that regulate the transcriptional activities of genes encoding proteins associated with the contractile apparatus. Mechanical plasticity of contractile-state smooth muscle further extends SMC functional diversity. This may also be regulated, in part, by the RhoA GTPase/ROCK pathway, via reorganization of cytoskeletal and contractile proteins. Future studies that define transcriptional and posttranscriptional mechanisms of SMC plasticity are necessary to fully understand the role of SMC in the pathogenesis and morbidity of human diseases of the airways, vasculature, and gastrointestinal tract.