Acute lymphoblastic leukemia (ALL) is now curable in 60-80% of children. In adults, in spite of adopting treatment protocols based on therapy for childhood ALL, the disease is still curable in 30-40% of patients only. These worse results of therapy may be due to the induction of various cell defence mechanisms, such as activation of P-glycoprotein, which protects man against xenobiotics. Among a number of various multi-drug resistance mechanisms, differences between adults and children with ALL have been found only for higher P-glycoprotein expression and possibly more often p53 gene mutations in adults. Induction of expression of drug resistance proteins during chemotherapy and co-existence of various mechanisms are common phenomena in adult ALL. Differences in resistance to different drugs might contribute to the impact of age on the outcome of ALL. The underlying mechanisms for these differences are still largely unknown; however, knowledge about drug resistance mechanisms can lead to new therapeutic options.