The trend towards community-based mental health services and the de-institutionalization of psychiatric patients has led to a clear shift of the caring burden from health and welfare services to the families. Studies that have addressed the effect of this burden on caregivers have mostly focused on the extent of psychological distress and its link with the psychiatric patient; only a few have addressed the risk that caregivers run of is two to three times higher in caregivers of psychiatric patients than in the general population. In particular, there is evidence that the rate of depressive symptoms among caregivers of severe psychiatric patients ranges from 38% to 60%; these family members often go untreated. There is a great need for intervention and research in this field, in order to effectively prevent and treat depressive symptoms and reduce burden in caregivers. We developed a manualized treatment program, based on a cognitive-behavioural approach and administered in two different group conditions, namely psychotherapy and mutual support. In this paper, we examine the relative efficacy of group cognitive-behavioral therapy (CBT) and mutual support group therapy (MST) in reducing depressive symptoms and caring burden. Caregivers depressed or at risk of depression (N = 40) were randomly assigned to a CBT or a MST group, led respectively by 2 psychotherapists and 1 psychologist-facilitator. Before and after intervention, all participants were individually assessed with the Beck Depression Inventory and Family Problems questionnaire. Both the CBT and MST therapies produced reductions in depression score, though in the MST groups the trend was not significant. Nevertheless, analysis of the clinical significance of change in the BDI score for each subject showed an improvement in 58.3% of depressed caregivers treated with CBT and in 45.4% of those treated with MST. Differently from CBT, MST produced an improvement in two dimensions of family burden.