Phytochemicals have consistently served as effective agents in the fight against numerous diseases. Flavonoids are a category of plant-derived compounds that exhibit a wide range of health-related effects. Among these, flavonols are well-documented molecules for both cancer prevention and therapy, as they have demonstrated a broad range of pharmacological applications in cancer research. In this chapter, we present a synthesis of recent and significant evidence regarding the anticancer activity of the main flavonols. Overall, flavonols are promising compounds due to their multi-target potential; therefore, further research is strongly encouraged to adequately define their pharmacotoxicological profile and evaluate their potential use as adjuvant and chemoprevention therapies.