Critical physiological roles of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) include the regulation glucose and lipid homeostasis, cellular differentiation, and modulation of inflammation. The potential for targeting PPARβ/δ for the prevention and treatment of metabolic diseases or cancer, is compromised because of major inconsistencies in the literature. This is due primarily to uncertainty regarding the effect of PPARβ/δ and its activation on cell proliferation, apoptosis and cell survival. This review summarizes both the confirmed and conflicting mechanisms that have been described for PPARβ/δ and the potential for targeting this nuclear receptor for the prevention and treatment of colon cancer.