Quality of life (QOL) is recognized as a key outcome of chronic health conditions and is increasingly used and recommended for clinical care and clinical trials. Neurocognitive developmental disorders and disabilities (NDD) are characterized by impairments or comorbidities in multiple areas of function, and, unsurprisingly, youth with NDD and their families have poorer QOL relative to their peers. The impact of NDD goes beyond the characteristic symptoms of the illness, and youth with NDD face numerous comorbidities and psychosocial problems that may have a large impact on QOL. In this chapter, first, we discuss the varying approaches and methodological considerations associated with the measurement of QOL and the implications of using "generic," "disease-specific," and proxy-reported measures of QOL. Second, we review the literature evaluating the QOL of youth with various NDD relative to healthy controls and factors associated with outcomes. Last, we conclude with a review of the literature outlining the importance of family environment, the compromised QOL of parents of youth with NDD, and the needs of parents. Evaluation of QOL is an important and recommended component of comprehensive care and clinical trials.