Objective. To examine physical, cognitive, and social-emotional predictors of quality of life (HRQOL) and functional disability (FD) in adolescents diagnosed with Neurofibromatosis-1. Methods. Participants were twenty-seven adolescents with a diagnosis of NF-1 who were recruited through an NF-1 specialty clinic at a large Midwestern children's hospital. Measurements of the adolescents' cognitive functioning, pain, FD, HRQOL, and social and emotional functioning were obtained with corresponding parent measures. Results. Emotional functioning significantly predicted youth-reported and parent-reported HRQOL, whereas days of pain significantly predicted youth-reported FD. Conclusions. NF-1 is a complex disease. Measurements of the overall impact of the disease tap into different aspects of the effects of NF-1 on daily life. Global outcomes such as HRQOL appear to be influenced especially by emotional functioning, whereas outcomes such as FD appear to be influenced by the physical/organic aspects of NF-1.