To evaluate treatment outcomes in children with acute lymphoblastic leukemia (ALL) over the past 3 decades, we assessed the survival of children with ALL in the Surveillance, Epidemiology, and End Results (SEER) database. Among 12,096 patients from 18 SEER sites diagnosed from 1981 to 2010, survival rates improved each decade from 74.8% to 84.5% to 88.6% at 5 years and from 69.3% to 80.9% to 85.5% at 10 years (P < 0.0001). For ages 10-14 years, 10-year survival increased by more than 20 percentage points to 75.3%, but for infants, it remained low at 54.7%. Improvements in survival rates were observed in both sexes, but survival rates were higher in girls than in boys. For ages 0-14 years during the 2001-2010 period, the 10-year relative survival rates were 87.8% in girls and 83.6% in boys (P < 0.01). Survival rates in child with ALL are expected to further improve with continuous advance in therapies such as targeted therapy and personalized therapy.