The aim of the present study is to identify the relative contribution of patient and caregiver characteristics in a sample of primary carers of patients with chronic mental disorders living in the community. As carers were recruited from caregiver organizations, mainly mothers of an adult child suffering from schizophrenia participated in the study (n = 102). Within a comprehensive transactional stress model, burden was assessed with respect to objective and subjective burden, cognitive-emotional well-being, psychological distress and subjective quality of life. Primary stressors include illness-related characteristics of the patient, and a number of personal dispositions and resources of the caregivers were included as potential moderating variables. Multiple regression analyses were separately calculated for each dimension of burden. Interaction of carers’ expressed emotion and external locus of control with the patient’s problem with family communication as well as perceived social support was most predictive for objective and subjective burden, whereas carers’ neuroticism appeared as the most relevant predictor of their well-being, psychological distress and subjective quality of life. Among the patients’ variables, regular employment contributed significantly to reduce carers’ distress and enhance their well-being. As the sample was recruited from caregiver organizations, a selection bias has to be taken into account. To reduce caregiver burden, especially mothers’ burden, the patients’ occupational abilities should be strongly enhanced at an early stage. Family interventions should improve dysfunctional interactions, enhance the carers’ social activities and focus more intensely on the carers’ own dispositions.