Peroxisome proliferator-activated receptor γ (PPAR-γ) belongs to the family of nuclear hormone receptors (NHRs) and is a ligand-activated transcription factor. There are four mRNAs, PPAR-γ1, PPAR-γ2, PPAR-γ3 and PPAR-γ4, which encode two proteins, PPAR-γ1and PPAR-γ2. PPAR-γ consists of five or six structural regions (A–F) in four functional domains. The NH2-terminal A/B domain harbors a ligand-independent transcriptional activation function (AF-1), the C domain is a DNA binding domain (DBD), the D hinge region is important for co-factor docking and the complex multifunctional COOH-terminal portion (E/F) encompasses the ligand binding domain (LBD), a dimerization interface and the ligand-dependent activation domain AF-2. Some long-chain polyunsaturated fatty acids, arachidonic acid metabolites and fatty acid derived components are natural ligands of PPAR-γ. The anti-diabetic thiazolidinedione class of drugs, certain non-steroidal anti-inflammatory drugs (NSAIDs) and some non-thiazolidinedione tyrosine are the synthetic ligands of PPAR-γ. After activation, it forms heterodimer with the retinoid X receptor (RXR) and then binds to specific recognition sites in the target gene, the peroxisome proliferator response elements (PPREs), and regulates transcription of specific genes. PPAR-γ has potential anti-neoplastic effects both in solid cancer and in leukemia through inhibition of cell proliferation, induction of apoptosis and terminal differentiation, as well as inhibition of angiogenesis. The ligands of PPAR-γ may represent a promising, novel therapeutic approach for certain human malignancies.