The multidrug-resistance (MDR) phenotype expressed in mammalian cell lines is complex. A cell selected with a single agent can acquire cross-resistance to a remarkably wide range of compounds which have no structural or functional similarities. The basis for cross-resistance seems to be a decreased net cellular accumulation of the drugs involved, and has been attributed to alterations in plasma membrane. An over-expressed plasma membrane P glycoprotein of relative molecular mass of 170 kD (Pgp) is consistently found in different MDR human and animal cell lines, and in transplantable tumors. Consequently, it has been postulated that Pgp directly or indirectly mediates MDR. This paper reviews the current knowledge on etiology, pathogenesis, diagnosis and therapy of MDR.