PURPOSE: We investigated the effect of parents' mental health, life events, and home life (among other factors) on adolescents'/youths' mental health, whether such an effect varies when several variables are assessed jointly, and also whether the informant source of the mental health problem modifies the estimations. METHODS: We studied a representative sample of 454 Spanish adolescents/youths studied longitudinally (2 assessments, 3 years apart). We considered factors associated with adolescents'/youths' mental health (conduct, emotional, and hyperactivity scores [SDQ]): risk factors (parents' mental health and life events) and mediators (social and financial support). Structural equation modeling was applied. We constructed two models: (a) with parents' SDQ responses and (b) with self-reported SDQ responses (in a subsample of N = 260). RESULTS: Model fit was adequate for parents' appraisal. Parents' mental health (p < 0.05) and undesirable life events (p < 0.05) were the most important risk factors. The same model showed poorer fit when self-reported measures were used. Home life exerted a stronger protective effect on adolescents'/youths' mental health when reported by adolescents/youths. The negative effect of parents' mental health was significantly protected by home life in emotional [-0.14 (0.07)] and hyperactivity scores [-0.2 (0.08)]. CONCLUSIONS: Even in the presence of other factors, parents' mental health has an important effect on adolescents'/youths' mental health. Good levels of home life are protective, especially when adolescents'/youths' mental health is self-reported.