Serotonin is an important neurohormonal factor that has been implicated in cardiovascular function. It can regulate vascular tone, act directly on cardiomyocytes and stimulate chemosensitive nerves in the heart. Cardiovascular dysfunction is observed when serotonin signaling is altered or when variation in serotonin concentration occurs. Recent studies have provided evidence that, in the absence of peripheral serotonin synthesis, blood serotonin (which is almost exclusively stored in platelets) is markedly reduced, and that this drop leads to heart failure. This implies that the level of circulating serotonin is a key factor in maintaining normal cardiovascular activity. These findings offer new prospects for the use of serotonin in therapies for cardiovascular diseases.