Decades of research have confirmed that being a family caregiver is a stressful role. However, the point at which these stressors constitute a real risk for decreased mental health has not been established. The purpose of the present study was to determine a statistically valid cut-off score for the Zarit Burden Interview (ZBI) in order to identify family caregivers at risk for depression and in need of further assessment and intervention. The ZBI and the Geriatric Depression Scale or the CES-D were administered to three different populations of family caregivers of older adults: stroke caregivers (n=80), chronic obstructive pulmonary disease (COPD) caregivers (n=48), and general disability caregivers (n=70). Using three different statistical methods, a ZBI cut-off score was determined. Next, contingency analysis was used to compare depression scale scores and ZBI cut-offs for the three groups of caregivers. Findings suggest that a cut-off score ranging from 24-26 has significant predictive validity for identifying caregivers at risk for depression. A ZBI cut-off of 24 correctly identified 72% of caregivers with probable depression. The validity of ZBI cut-offs scores warrants further confirmation with larger samples. Valid cut-off scores would enable health care providers to assess family caregivers at risk and provide necessary interventions to improve their quality of life in this important role.