Smooth muscles are widely distributed in mammal body through various systems such as circulatory, respiratory, gastro-intestinal and urogenital systems. The smooth muscle cell (SMC) is not only a contractile cell but is able to perform other important functions such as migration, proliferation, production of cytokines, chemokines, extracellular matrix proteins, growth factors and cell surface adhesion molecules. Thus, SMC appears today as a fascinating cell with remarkable plasticity that contributes to its roles in physiology and disease. Most of the SMC functions are dependent on a key event: the increase in intracellular calcium concentration (Ca(2+)). Calcium entry from the extracellular space is a major step in the elevation of Ca(2+) in SMC and involves a variety of plasmalemmal calcium channels, among them is the superfamily of transient receptor potential (TRP) proteins. TRPC (canonical), TRPM (melastatin), TRPV (vanilloid) and TRPP (polycystin), are widely expressed in both visceral (airways, gastrointestinal tract, uterus) and vascular (systemic and pulmonary circulation) smooth muscles. Mainly, TRPC, TRPV and TRPM are implicated in a variety of physiological and pathophysiological processes such as: SMC contraction, relaxation, growth, migration and proliferation; control of blood pressure, arterial myogenic tone, pulmonary hypertension, intestinal motility, gastric acidity, uterine activity during parturition and labor. Thus it is becoming evident that TRP are major element of SMC calcium homeostasis and, thus, appear as novel drug targets for a better management of diseases originating from SMC dysfunction.