This study distinguished between factors that were protective for children at high risk and those that were resources for children regardless of risk level and determined the generality of these factors across three different risk definitions: school-age children of mothers with (a) unipolar depression (n = 22), (b) bipolar disorder (n = 18), and (c) medical illness (n = 18), each compared to a low-risk control group (n = 38). Results were verified at a 1-year follow-up. Positive self-concept, academic success, social competence, and positive perceptions of the mothers were resource factors associated with lower diagnostic ratings for children in all risk groups. Maternal social competence and having a healthy father in the home were resource factors for maternal unipolar risk but, unexpectedly, were vulnerability factors for maternal bipolar risk. Children's friendships were protective for children of medically ill mothers; however, frequent contact with an adult friend was a risk factor for unipolar offspring. The latter finding suggests that such contact might be a consequence of poor parent-child relationships. Findings are discussed in terms of possible interventions for children at risk, and suggestions for additional research are offered.