Significant numbers of children and adolescents with acute lymphoblastic leukemia (ALL) do not adequately adhere to their treatment regimen. Failure to take the appropriate amount of prescribed medication may result in disease relapse. Although a number of research studies have sought to identify the factors associated with medication nonadherence in this group, no systematic study has sought to evaluate the efficacy of intervention packages in improving adherence. The aim of the current paper is to provide an overview of the research investigating treatment adherence in ALL patients and to identify the relevant risk factors associated with reduced adherence with medication. The paper will further discuss the role of psychologic therapy in improving treatment adherence in children and adolescents with ALL, with a particular focus on identifying the need for controlled outcome studies.