Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio‐emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers’ perspectives, in predicting medication non‐adherence for adolescents (ages 12‐19 years) 1 year post‐transplant. Non‐adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers’ perceptions of poorer overall family functioning predicted missed medication doses (ΔR2 = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem‐solving (β = −0.795, t(21) = −2.927, P = 0.008) and affective involvement (β = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR2 = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family‐based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.