Cancer is the second leading cause for mortality in US only after heart disease and lacks a good or effective therapeutic paradigm. Despite the emergence of new, targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is supporting the idea that human cancers can be considered as a stem cell disease. Malignancies are believed to originate from a fraction of cancer cells that show self renewal and pluripotency and are capable of initiating and sustaining tumor growth. The cancer-initiating cells or cancer stem cells were originally identified in hematological malignancies but is now being recognized in several solid tumors. The hypothesis of stem cell-driven tumorigenesis raises questions as to whether the current treatments, most of which require rapidly dividing cells are able to efficiently target these slow cycling tumorigenic cells. Recent characterization of cancer stem cells should lead to the identification of key signaling pathways that may make cancer stem cells vulnerable to therapeutic interventions that target drug-effluxing capabilities, anti-apoptotic mechanisms, and induction of differentiation. Dietary phytochemicals possess anti-cancer properties and represent a promising approach for the prevention and treatment of many cancers.