Acute lymphoblastic leukemia is the most important childhood cancer. Multidrug resistance is an important factor of poor prognosis. We present the P-glycoprotein (P-gp) activity in 2 patients with different outcomes. Both patients had B-cell acute lymphoblastic leukemia; they were responding properly to the treatment, but one of them had an increment in the P-gp activity that correlates with an increment in the disease manifestation, the patient had to be hospitalized and developed sepsis and subsequently died. P-gp levels were correlated with disease progression. P-gp activity needs to be evaluated during treatment to assess and prevent disease relapse or the patient´s death.