This study examined a group of participants who were fully remitted from a previous episode of major depressive disorder, and evaluated the role of cognitive and emotional reactivity to a mood challenge, and life stress in the prediction of relapse. Fifty-two participants were evaluated during remission, and their reactivity (i.e., change in dysfunctional attitudes and emotional state) to a depressed mood induction was evaluated. The cohort was followed up 12 months after the initial assessment. Thirty-five percent of the sample experienced a relapse during the follow-up period. Relapse was predicted by higher rates of life stress, and lower levels of emotional reactivity (specifically less reduction in happiness) to the mood induction during the initial assessment. Cognitive reactivity to the mood induction did not predict relapse, nor did the interaction between cognitive reactivity and life stress. These findings are discussed in terms of recent literature suggesting that depression is associated with insensitivity to emotion context, such that depressed individuals display blunted emotional responses to affective stimuli, including sadness-inducing stimuli. These findings suggest that insensitivity to emotional context may also be a characteristic of euthymic individuals at risk of relapse.