Pigment epithelium-derived factor (PEDF) has roles in antiangiogenesis and antitumourigenesis that are intimately entwined and is showing promise as a potential anticancer agent. However, the function of PEDF in the deregulated apoptotic pathways of malignant cells must first be fully characterized. Here, we review the currently known apoptotic pathways that are relevant to PEDF and cancer. Recently, a pathway that includes the PEDF receptor, PPARgamma and p53 has emerged. It is hoped that further characterization of this and other pathways involved in cancer will bring to light potential new therapeutic targets and approaches, which due to their specificity might be free of the morbidity associated with conventional chemotherapy.