Protein tyrosine kinases play a fundamental role in signal transduction pathways regulating a number of cellular functions such as cell growth, differentiation and cell death. Tyrosine kinases are, therefore attractive targets for the design of new therapeutic agents, not only against cancer, but also against many other diseases. Numerous tyrosine kinase inhibitors have been discovered by screening of plant extracts based on ethnopharmacological and chemotaxonomical knowledge. Specific screening approaches have led to the isolation of structurally distinct classes of inhibitors, including phenylpropanes, chalcones, flavonoids, coumarins, styrenes, quinones and terpenes. These natural inhibitors have served as valuable leads for further design and synthesis of more active analogues. Many of these inhibitors have also been used in probing the molecular and cellular mechanisms involved in the protein tyrosine kinase mediated signal transduction. In this review, plant-derived protein tyrosine kinase inhibitors and their synthetic analogues were systematically evaluated based on their plant origin, structureactivity relationship and anticancer efficacy.