Transient Receptor Potential Canonical (TRPC) proteins are non-selective cation channels ubiquitously expressed throughout the cardiovascular system, where they participate as Ca2+/Na+ -permeable channels and/or signaling platforms in various physiological and pathophysiological mechanisms. TRPCs have been implicated in essential hypertension, cardiac hypertrophy and endothelial dysfunction. Despite these pathologies being related, directly or indirectly to development of atherosclerotic lesions, the potential role of TRPCs in the pathogenesis of atherosclerosis remains unexplored. Recent studies from our laboratory showing an obligatory requirement of TRPC3 in the inflammatory signaling linked to monocycle recruitment to coronary endothelium, suggest for the first time potential pathophysiological relevance of a member of the TRPC group in atherogenesis. This brings about the question whether we can envision TRPCs as potential targets for diagnosis, prognosis and/or treatment of atherosclerosis. Here we revisit some of the existing knowledge on TRPCs and cardiovascular pathology and discuss it within the context of cellular/molecular processes related to atherogenesis. Potential limitations and advantages of TRPCs as prospectives targets in atherosclerosis are discussed and confronted against those of channel blockers currently in use.