This study investigated religious commitment and resilience as predictors of depression among adolescents with physical challenges. It was hypothesized that religious commitment and resilience will significantly predict depression among adolescents with physical challenges.Participants in the study were 78 adolescents (41males and 37 females) with physical challenges who were drawn from three schools of special education in Enugu State and Anambra State in Southeast Nigeria. They were aged 12 to 21 years with mean age 15.92 years (SD = 2.79 years). The design was cross-sectional. Participants completed Religious Commitment Inventory (RCI -10), Resilience Scale (RS-14), and Self Rating Depressive Scale.Results showed that resilience was a significant negative predictor of depressive symptoms (β = .29, p < .05). Intrapersonal component of religious commitment did not significantly predict depressive symptoms (β = -.03, p < .01). Interpersonal religious commitment was a significant negative predictor of depressive symptoms (β = -.51, p < .001). It was concluded that depression may be best avoided or reduced in adolescents with physical challenges by building self-confidence and a sense of optimism in them before they enter this phase of their lives i.e. during childhood stage. Again adolescents with physical challenges are enhanced by their social experiences in religious environments or religious gathering than with their private practices and thus are advised to have confidants or a sufficient social network to avoid mental health difficulty