Adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) are recognized as a unique population with specific characteristics and needs. In adolescents age 15 to 20 years, the use of fully pediatric protocols is supported by many comparative studies of pediatric and adult cooperative groups. In young adults, growing evidence suggests that pediatric-inspired or even fully pediatric approaches may also dramatically improve outcomes, leading to long-term survival rates of almost 70%, despite diminishing indications of hematopoietic stem-cell transplantation. In the last decade, better knowledge of the ALL oncogenic landscape according to age distribution and minimal residual disease assessments has improved risk stratification. New targets have emerged, mostly in the heterogeneous B-other group, particularly in the Philadelphia-like ALL subgroup, which requires both in-depth molecular investigations and specific evaluations of targeted treatments. The remaining gap in the excellent results reported in children has many other contributing factors that should not be underestimated, including late or difficult access to care and/or trials, increased acute toxicities, and poor adherence to treatment. Specific programs should be designed to take into account those factors and finally ameliorate survival and quality of life for AYAs with ALL.