The objectives in this special issue are (1) to critically review current information on the mechanisms coupling extracellular regulatory signals to regulation of cross-bridge cycling and proliferation in smooth muscle, and (2) identify significant gaps or unresolved issues that are important topics for future research. The experimental and analytical difficulties discussed above are increasingly recognized and surmounted. Elucidation of the molecular and cellular events underlying the biologal properties of smooth muscle is in the midst of a period of rapid progress. While the reviews reveal many gaps to be filled and illustrate areas of contention, they also capture the excitement of new discoveries.