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Our objective in this review is to summarize evidence of the strong cardiac rhythmicity-enhancing power of melatonin in the Drosophila melanogaster model system and discuss the implications of these findings in the context of fundamental cardiac pacemaker function and potential clinical applications. Drosophila has proven itself as an exceptional research organism given the far-reaching genetic and molecular tools it offers. We consider details of the fly's myogenic, ion-channel-based pacemaker and summarize aspects of its neurohomonal control. Melatonin, in the context of cardiology, has predominately been associated with its antioxidant properties in the prevention of reperfusion damage after infarct, but we have strongly confirmed the few reports of its effect strengthening rhythmicity. We discuss our clear results showing that melatonin is capable of converting normal noisy heartbeat to an extremely regular oscillator. It rescues the very uneven beat of the hearts of flies bearing a serious mutation in a gene encoding one of its core pacemaker ion channels. Possible mechanisms for these effects are considered.