Coumarins, an old class of compounds, are naturally occurring benzopyrene derivatives. A lot of coumarins have been identified from natural sources, especially green plants. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. Coumarins have attracted intense interest in recent years because of their diverse pharmacological properties. Among these properties, their cytotoxic effects were most extensively examined. In this review, their broad range of effects on the tumors as shown by various in vitro and in vivo experiments and clinical studies are discussed. Hence, these cytotoxic coumarins represent an exploitable source of new anticancer agents, which might also help addressing side-toxicity and resistance phenomena. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. In this review, plant derived coumarins and their synthetic analogues were systematically evaluated based on their plant origin, structureactivity relationship and anticancer efficacy. Owing the their diverse effects and inconclusive results from different in vitro studies, the mechanism of their action is not yet fully understood and correlation of effects with chemical structures is not conclusive at the moment. It is the objective of this review to summarize experimental data for different coumarins, used as cytotoxic agents, because promising data have been reported for a series of these agents. Yet, the results from different coumarins with various tumor lines are contradictory in part. We therefore conclude that there is still a long way to go until we know which cytotoxic agent will clinically be suitable for what tumor entity for treatment. Their ability to bind metal ions represents an additional means of modulating their pharmacological responses.