Increased consumption of fruit and vegetables can represent an easy strategy to significantly reduce the incidence of cancer. We recently demonstrated that the flavonoid quercetin, naturally present in the diet and belonging to the class of phytochemicals, is able to sensitize several leukemia cell lines and B cells isolated from patients affected by chronic lymphocytic leukemia (B-CLL), in addition to apoptotic inducers (anti-CD95 and rTRAIL). Further, it potentiates the effect of fludarabine, a first-line chemotherapeutic drug used against CLL. The proapoptotic activity of quercetin in cell lines and B-CLL is related to the expression and activity of Mcl-1–antiapoptotic proteins belonging to the Bcl-2 family. Quercetin downregulates Mcl-1 mRNA and protein levels acting on mRNA stability and protein degradation. Considering the low toxicity of the flavonoids toward normal peripheral blood cells, our experimental results are in favor of a potential use of quercetin in adjuvant chemotherapy in CLL or other types of cancer.