5-HT has profound effects on cardiac rate and force in a variety of animal species, including humans. The main initial response to 5-HT is a short-lasting bradycardia, mediated via a Bezold-Jarisch-like reflex, and initiated by stimulation of 5-HT3 receptors present on cardiac vagal afferents. Once this bradycardia is suppressed, 5-HT induces cardiac stimulation which, true to its chameleonic nature described here by Pramod Saxena and Carlos Villalon, is mediated by different mechanisms and receptors in different species. In several species, including humans, coronary vasodilatation is mediated by 5-HT1-like receptors, while both 5-HT1-like and 5-HT2 receptors mediate vasoconstriction. This knowledge may lead to a better assessment of the possible role of 5-HT in cardiovascular pathologies and to the development of selective 5-HT receptor agonists and antagonists for therapeutic usefulness in heart failure, coronary vasospasm and to avoid potential cardiac side-effects.