Depression is the most frequent psychiatric disorder and has long-term, compromising effects on the mother-infant relationship and the child's development. The infant continuously faces a climate of negative affect that disrupts the interactive experience of the infant and the mother. This article presents findings on the impact of maternal depression on the infant affective state and the specific interactive patterns associated with infant affect regulation. Mother-infant interactions were studied using microanalytic, second-by-second methods in the laboratory and also by using naturalistic home observations. The empirical findings highlight the impact of maternal depression on the infant affective state and on the capacity for repairing states of miscoordination. The impact is seen not only in severely and acutely depressed mothers, but in mothers who have only high levels of depressive symptoms. These infants develop negative affective states that bias their interactions with others and exacerbate their affective problems. Further findings with regard to gender-specific effects show that male infants are more vulnerable than female infants to maternal depression. The findings point out the need for therapeutic interventions that focus on the mother-infant dyad and infant affective state in the treatment of maternal depression.