Ever since the discovery 20 years ago that the transforming retroviral v-sis oncogene is derived from the platelet-derived growth factor (PDGF) B chain gene, PDGF signaling has been an interesting target for cancer treatment. In addition to its role in autocrine growth stimulation of tumor cells, PDGF has also been suggested to regulate tumor stroma fibroblasts and tumor angiogenesis (Figure 1). The occurrence of clinically useful PDGF receptor antagonists, like Glivec (STI571/Gleevec), now allows for an evaluation of the importance of PDGF receptor signaling in malignancies (Buchdunger et al, 1996; Capdeville et al., 2002). This review summarizes the biology of PDGF and discusses the role of PDGF receptor expression in different tumor compartments. Two sets of recent findings are particularly emphasized: the first set demonstrates clinical responses to PDGF antagonists in autocrine settings, and the second set presents beneficial effects of targeting PDGF receptors in the tumor stroma in animal models.