Evidence suggests that the left frontal region is specialized for the expression of positive emotions, such as joy, whereas the right frontal region is specialized for certain negative emotions, such as distress. We previously reported that infants of mothers with depressive symptoms exhibited atypical patterns of frontal electroencephalographic (EEG) activity. We now extend these findings by examining the combined influence of maternal depression and attachment security on the infant's behavior and brain activity. Participants were 26 infants, 11–17 months of age, and their mothers. Twelve mothers reported elevated levels of depressive symptoms. Attachment behavior was observed in the traditional Strange Situation. While left and right, frontal and parietal EEG was recorded, infants were exposed to a baseline and three emotion-eliciting conditions (play with mother, stranger approach, maternal separation). During baseline and the condition designed to elicit positive emotion (play with mother), securely attached infants of symptomatic mothers exhibited reduced left frontal brain activity, compared to securely attached infants of nonsymptomatic mothers. During maternal separation, the most robust finding was that infants of symptomatic mothers, regardless of their attachment classification, exhibited reduced right frontal activity and lower levels of behavioral distress. The results suggest that both the mother's emotional well-being and her attachment relationship with her infant can influence infant frontal brain activity and affective behavior.