An overview of the current mechanisms identified as associated with the expression of multidrug resistance is provided. The clinical relevance of multidrug resistance associated with the overexpression of the three major drug resistance-associated proteins namely, P-glycoprotein, MRP and/or LRP, is discussed. Alternate forms of multidrug resistance involving the reduced or altered expression of either or both of the topoisomerases is next considered, followed by a short section relating to resistance to the platinum complexes and the contribution of altered DNA repair. For those involved in new drug discovery programmes for cancer chemotherapy, the identification and study of these new major intracellular targets makes this an exciting era.