Objective During adolescence, the significance of peer relationships peaks, and the presence and quality of dyadic friendships impact psychosocial outcomes. Yet, friendships have been studied infrequently among youth with chronic illness, particularly youth with cystic fibrosis (CF). The current aims were to (1) describe friendships among adolescents with CF, including number, duration, frequency of interactions, and positive/negative friendship qualities, and (2) explore associations between friendship quality, treatment adherence, and health-related quality of life. Methods Participants (N = 42) reported on friendships with peers with and without CF; caregivers reported on adolescents’ adherence and quality of life. Results Friendships with CF-peers were less common and lower quality than friendships with non-CF peers. Both positive and negative friendship qualities were associated with adherence; positive friendship qualities were uniquely associated with quality of life. Conclusions CF-related health promotion efforts may benefit from addressing the impact of friendships on adherence and quality of life.