Heat shock protein 90 (Hsp90) is an ATP-dependent chaperone and a noteworthy component of cellular folding machinery in eukaryotes and bacteria. What makes Hsp90 specifically promising as a target for anti-cancer drugs is that many of its client proteins are involved in signaling and chromatin-remodeling pathways, and these pathways are often disrupted in many types of cancers. A very recent study by Lang et al. (Clin Cancer Res 2007; 13:6459-68) provide compelling evidence supporting a novel IL-6/STAT3/HIF-1alpha autocrine loop in pancreatic cancer cells, emphasizing the arresting role of Hsp90 inhibitors. Here, we discuss up-to-date advances towards the development of novel Hsp90 inhibitors designed to selectively block the growth and proliferation of tumor cells and proving to be intriguing targets for current clinical studies and cancer therapeutics.