Interactions of the anticancer drugs doxorubicin (DOX) and thaliblastine (TBL) with model membranes composed of neutral and negatively charged membrane phospholipids were studied. Drug-phospholipid interactions were measured by differential scanning calorimetry and nuclear magnetic resonance. The membrane activities of DOX and TBL were compared to those of the multidrug resistance (MDR) modulators trans-flupentixol and verapamil. The results suggest that DOX and TBL are membrane active drugs. The impact of the drug-membrane activity on MDR is discussed.