P-glycoprotein (P-gp) is an energy dependent drug pump responsible for multidrug resistance (MDR) in human cancers. While it is irrefutable that P-gp can efflux xenobiotics out of cells, the biological function of P-gp in multicellular organisms has yet to be firmly established. The question of what, if anything, P-gp does when not effluxing drugs has been raised by recent reports indicating that P-gp may regulate apoptosis, chloride channel activity, cholesterol metabolism and immune cell function. There is now a lively debate regarding the possible role of P-gp in regulating cell differentiation, proliferation and survival.