Many studies have reported on the adverse effects of maternal depression on offspring. Infants of depressed mothers are found to be more likely at risk to develop mental and socioemotional problems. In this study, an early intervention program is presented that aims to improve the interaction between depressed mothers and their infants to prevent developmental problems in the children. The program has recently been introduced in the Dutch Community Mental Health Centers as part of a national multicomponent program to reduce the risk of psychiatric and social problems in the offspring of parents with a mental disorder. The intervention for depressed mothers with babies is based on a transactional model in which the mother–child interaction plays a key role in explaining the development of socioemotional problems in the children. The model as discussed in the first part of this article addresses a range of evidenced-based parental, child, and contextual risk factors that effect the quality of the interactions between depressed mothers and their infants and that contribute to both vulnerability and resilience of the children during later childhood and adolescence. ©2005 Michigan Association for Infant Mental Health.