Serotonin acts solely via 5-HT₄-receptors to control human cardiac contractile function. The effects of serotonin via 5-HT₄-receptors lead to positive inotropic and chronotropic effects, as well as arrhythmias, in the human heart. In addition, 5-HT₄-receptors may play a role in sepsis, ischaemia, and reperfusion. These presumptive effects of 5-HT₄-receptors are the focus of the present review. We also discuss the formation and inactivation of serotonin in the body, namely, in the heart. We identify cardiovascular diseases where serotonin might play a causative or additional role. We address the mechanisms which 5-HT₄-receptors can use for cardiac signal transduction and their possible roles in cardiac diseases. We define areas where further research in this regard should be directed in the future, and identify animal models that might be generated to this end. Finally, we discuss in what regard 5-HT₄-receptor agonists or antagonists might be useful drugs that could enter clinical practice. Serotonin has been the target of many studies for decades; thus, we found it timely to summarise our current knowledge here.