Introduction: Long-term epidemiological studies have demonstrated that regular ingestion of flavonoids contained in dietary sources is associated with a reduced risk for many chronic diseases including cancer. However, although flavonoids are largely consumed in the diet and high concentrations may exist in the intestine after oral administration, the plasma/tissue concentrations of flavonoids are lower than their effective therapeutic doses due to poor bioavailability, resulting in the limited efficacy of flavonoids in various clinical studies. Therefore, the application of nanotechnology to deliver flavonoids to tumor sites has received considerable attention in recent years. Areas covered: In this review, after a general review of the potential benefits of flavonoids in cancer therapy and several key factors affecting their bioavailability, the current efforts in improving the delivery efficacy of promising candidates that are particularly important in the human diet, namely quercetin, epigallocatechin-3-gallate (EGCG) and genistein were focused on. Finally, the challenges of developing flavonoid delivery systems that improve flavonoid bioavailability and their anticancer therapy potentials were summarized. Expert opinion: The design of suitable molecular carriers for flavonoids is an area of research that is in rapid progress. A large number of unheeded promising favonoids are suffering from poor in vivo parameters, their potential benefits deserves further research. Furthermore, more effort should be placed on developing active targeting systems, evaluating the efficacy and toxicity of novel flavonoid delivery systems through small and large scale clinical trials. © 2013 Informa UK, Ltd.