In recent years, an increasing number of studies on the quality of life (QoL) of adults and children have been published, mostly describing outcomes of various medical conditions. Yet, despite the wide interest, there is no universal consensus even on the very definition of what constitutes QoL, particularly for children. Herein, we discuss the conceptual framework and operational definitions of QoL and health-related quality of life (HRQL), address some methodological issues, and review the literature on QoL studies among premature infants. We also describe areas of research that are likely to be fruitful in advancing the consideration of QoL in future studies and in clinical practice.