Objectives: Research has demonstrated that serving in the caregiver role is often associated with increased symptoms of depression, stress, and anxiety, but some people fare better than others in managing the burden of caregiving. The goal of the present study was to examine the potential moderating role of goal adjustment (the ability to disengage from unattainable goals and reengage in alterative ones) on the relation between caregiver burden and distress in family caregivers of cancer patients. Methods: Caregivers of adult family members diagnosed with cancer in the past 3 years participated (N = 102). Participants were consented and completed online questionnaires on psychological distress, caregiver burden, and goal adjustment. Results: The ability to disengage from unattainable goals was associated with lower anxiety and stress in the face of increasing caregiver burden. By contrast, the ability to reengage in alternative goals was associated with lower depression as burden increased. Conclusions: The present study suggests that goal adjustment may play an important moderating role in the relationship between caregiver burden and distress. Caregivers who are better able to disengage from unattainable goals may experience less stress and anxiety, and caregivers who are better able to reengage in alternative goals experience less depressed mood. This study provides preliminary evidence that learning different ways to approach and adjust goals may reduce depression, anxiety, and stress in family caregivers.