Natural products have been the source of many drugs used in modern therapeutics, and particularly in the case of anticancer drugs, more than 50 % originally came from natural products. Their importance as a source of leads for new drugs therefore cannot be underestimated. However, due to the painstaking way of conventional lead-finding, the attention towards natural products has been deviated in the last decades. A new strategy for the detection of active compounds is necessary to get natural product research out of its stalemate. Metabolomics, with its holistic approach and the possibility it provides for the simultaneous detection of all sorts of metabolites, has the potential to be instrumental for this new approach. Therefore, this review aims at providing examples that illustrate the possibilities of using metabolomics as a tool to find active compounds from natural products, specifically anticancer drugs. Two different methods, IN SILICO and IN SITU, have been introduced as possible approaches. Current methods to detect anticancer activity in natural products have been briefly reviewed and compared in the first section, and various applications of metabolomics in cancer research are mentioned as they can provide comprehensive information of cancer metabolites utilized in the IN SITU approach. Metabolomics will certainly improve the efficiency of lead-finding from natural products and thus reinstate this prolific source of potential anticancer drugs.