P-glycoprotein, the founding member of the ATP-binding cassette (ABC) family of drug transporters, was first identified almost three decades ago and shown to confer resistance to multiple chemotherapeutic agents when overexpressed in human tumors. Subsequent years have witnessed a tremendous effort to characterize the function and regulation of P-glycoprotein, initially spurred by the hope that its inhibition was the key to overcoming clinical resistance to multiple anticancer agents. However, the identification of MRP1, another member of the ABC drug transporter family, led to the realization that the multidrug resistance (MDR) phenotype is considerably more complex than initially believed. Indeed, at the present time at least 10 members of the ABC transporter family have been implicated in an MDR phenotype, and it is likely that more will be added to this list as studies progress. With this complexity comes the imperative to improve our understanding of the function of individual transporters, as well as to delineate the mechanisms underlying their expression in normal and tumor cells, particularly those that may be amenable to therapeutic intervention. Several articles within this volume address the structure and function of drug transporters. This review will focus on our current understanding of the regulation of ABC drug transporters at the level of transcription.