Nicotine is the main ingredient of smoking cessation therapies and electronic cigarettes. New to the market, electronic cigarettes, which are not regulated by Food and Drug Administration (FDA), have been marketed as the safe and alternative approach to cigarette smoking. Although containing significantly fewer amounts of toxic chemicals, electronic cigarettes, as well as other nicotine replacement therapies, still present additional health hazards due to significant nicotine exposure. The effects of nicotine exposure on musculoskeletal health have been extensively studied, but the mechanisms behind these effects are still unknown. Current research, however, suggests that these effects are mediated by the nicotinic acetylcholine receptors (nAChRs) of the musculoskeletal system. These receptors, which are activated in the presence of nicotine, undergo conformational changes that eventually alter the ionic permeability of their respective membranes. The results of these actions are linked to changes in cell proliferation, differentiation and microRNA expression.