Support from best friends is an important interpersonal factor in adolescent depression development but is often studied from an individual perspective in which dyadic effects are overlooked. This study aims to a) test whether differences in support vary at the individual level and are related to individual differences in the development of depressive symptoms, whether these differences vary at the dyadic level and are related to dyadic depression symptom development, or both, b) explore whether these associations are moderated by initial levels of depressive symptoms on the individual and/or dyadic level. Data from 452 adolescents (Mage = 13.03), nested in 226 same-gender friendship dyads (60.6% boy-dyads) who participated in the RADAR-Y project were included. Best friends self-reported annually (2006–2008; 3 waves) on their own depressive symptoms and perceived support from their friend. Multilevel models showed no direct association between support and depression development on the individual or dyadic level. However, the initial level of dyads’ depressive symptoms moderated the association between dyadic support and dyads’ subsequent depression symptom development. When dyads experienced relatively more initial depressive symptoms, higher levels of dyadic support were associated with relative increasing dyadic depressive symptoms. When dyads experienced relatively few initial depressive symptoms, higher levels of dyadic support were associated with relative decreasing dyadic depressive symptoms. Findings suggest that support from best friends can either protect against or exacerbate the development of depressive symptoms for friends, depending on the initial level of depressive symptoms of the dyad.