Multidrug resistance is a generic term for the variety of strategies that tumor cells develop to evade the cytotoxic effects of anticancer drugs. It is characterized by decreased cellular sensitivity, not only to the drug(s) employed in chemotherapy but also to a broad spectrum of drugs with neither obvious common targets nor structural homology. It is one of the major obstacles to the successful treatment of tumors. This review concentrates on some of the physiological changes observed in drug-sensitive and drug-resistant tumor cell lines that could account for their relative sensitivities to chemotherapeutics. These changes suggest alternative strategies for combating tumor cells in general and multidrug-resistant cells in particular.