Nonadherence to medical recommendations is a widespread problem well documented in a multitude of clinical settings. Nonadherence may adversely affect clinical outcomes such as survival and quality of life and increase health-care-related costs. An understanding of the factors driving nonadherence is key to developing effective adherence-enhancing interventions (AEIs). There are ongoing attempts in contemporary adherence research to better define the various components of adherence, to find optimal measures of adherence and correlations with clinical outcomes, and to create a classification system for AEIs. Nonadherence is also widely prevalent among adolescents and young adults (AYAs) with chronic hematological diseases, affecting up to 50% of patients and increasing with age. Combined use of objective (i.e. electronic monitoring, EM) and subjective (i.e. self-report) measures of adherence may be the preferred approach to assess adherence. The unique physical, social and emotional aspects of the AYA life stage are closely related to intricate causes of nonadherence in AYAs such as problems in transition to adult care. Until proven otherwise, the empirical target in AYAs with hematological disorders should be perfect adherence. Multilevel AEIs, EM feedback and behavioral interventions are among the most effective types of AEIs. Despite the magnitude of the problem, only a handful of AEIs have been evaluated among AYAs with hematological disorders. Thus, this is a field with unmet needs warranting high-quality trials using standardized and well-specified assessment methods and interventions. This review discusses the prevalence, definition, causes and clinical implications of nonadherence among AYAs with hematological disorders, along with strategies to measure and improve adherence.