This study examined caregiver strain (i.e., burden of care, caregiver burden) among families of adolescents in treatment for substance abuse disorders compared to youth with mental health problems. We used descriptive and regression analyses to compare groups and to examine the youth and family variables associated with caregiver strain across the two samples. The caregivers of the two groups of youth reported similar levels and types of caregiver strain at the subscale and item levels. In addition, there were similar patterns among the variables that predicted two of three dimensions of caregiver strain. We conclude that attending to caregiver strain in both substance abuse treatment and research is indicated.