A review of the literature has been undertaken to examine health-related quality-of-life (HRQoL) of children and adolescents with speech and language difficulties (SaLD), with a particular focus on evidence regarding the domains of HRQoL most affected by SaLD. Twelve electronic databases were searched for articles on this topic published from 1966 to January 2011. Seven studies suitable for inclusion were identified. These papers were reviewed in relation to their participants, sample size, study design, and outcome measures, which differed considerably across studies. From the studies reviewed, there is emerging evidence that HRQoL can be compromised for children and adolescents with SaLD relative to their peers, and some consensus that the social domain of HRQoL is most impacted. Overall, the review highlights a paucity of research in this area and recommendations are made as to how research may advance. Most importantly, studies examining the effect of child and family factors in mediating or moderating the relationship between SaLD and HRQoL are required. This knowledge will support the identification of children with SaLD at risk of poorer HRQoL outcomes and inform intervention strategies through the identification of relevant risk and protective factors.