ATPases have long been suggested as attractive drug targets. Designing small molecule, ATP competitive inhibitors, akin to that used to target protein kinases, is an appealing strategy for ATPase drug discovery. This approach has been highly successful for the molecular chaperone heat shock protein (Hspa ) 90, resulting in multiple inhibitors entering clinical trials for the treatment of cancer. Despite its strong validation as a potential anticancer target, discovery and development of ATP competitive, small molecule inhibitors of another molecular chaperone, Hsp70, have been less successful. Our experience of drug discovery efforts targeting both Hsp90 and Hsp70 will be used to suggest how structural features of the ATP binding site, fragment hit rate, and affinity for ATP could be used to assess the "druggability" of other ATPases and ATP binding sites.