Schematic representation of diverse intracellular signaling cascades which can be impacted upon hsp90 inhibition, and of examples of multiple molecular levels where these effects can occur (through effects on expression/function of hsp90 client proteins and/or their downstream effectors). Solid arrows indicate activation and dashed lines indicate inhibitory events. Hsp90 inhibitors of the ansamycin family specifically inhibit hsp90, but the highly pleiotropic roles of their target confer to this class of agents the advantage of simultaneous blockade, by a single chemical entity, of diverse pathways implicated in tumor cell proliferation, survival, drug resistance, and microenvironmental interactions. This multifactorial activity of hsp90 inhibitors provides a framework for use of these agents to counteract mechanisms of resistance to multiple other agents, and increase tumor cell sensitivity to diverse conventional and novel agents.