Cancer is one of the largest causes of morbimortality in the world and due to its prevalence the discovery of novel anticancer drugs in of great importance. The past century brought great advances in the field of plant and microbiology research, with the development of several compounds used in cancer treatment protocols. Many successful anticancer drugs that are in clinical use and have demonstrated significant efficacy are derived from natural products as plants, marine organisms, and microorganisms. With the recent advances in proteomics and metabolomics, there was a boost in the identification of new therapeutic targets offering new therapeutic perspectives. More than 50% of the total molecules approved between 1981–2014 are either natural product or derived from this, with the majority acting as antitumor agents. In this context, natural products have been acknowledged as abundant and successful sources for development of new anticancer therapies. The present review emphasizes the importance of the discovery of new plant-derived metabolites for use in cancer therapeutics and highlights the anticarcinogenic potential of natural products. The most important natural-derived drugs launched on the pharmaceutical market are also discussed.