In this article we review the evolution of cancer research involving PPARgamma, including mechanisms, target genes, and clinical applications. For the last thirteen years, the effects of PPARgamma activity on tumor biology have been studied intensely. Most of this research has focused upon the potential for employing agonists of this nuclear receptor in cancer treatment. As a monotherapy such agonists have shown little success in clinical trials, while they have shown promise as components of combination treatments both in culture and in animal models. Other investigations have explored a possible role for PPARgamma as a tumor suppressor, and as an inducer of differentiation of cancer stem cells. Whereas early studies have yielded variable conclusions regarding the prevalence of PPARgamma mutations in cancer, the protein level of this receptor has been more recently identified as a significant prognostic marker. We predict that indicators of PPARgamma activity may also serve as predictive markers for tailoring treatments.