This study analyzes guilt among family caregivers of dependent patients, from a gender perspective. A qualitative design was used, conducting in-depth interviews and focus groups. Using purposive sampling, we selected 73 family caregivers and 23 health professionals (family medicine, community nursing, and social work) from the Primary Care District of Seville. The content of the information collected was analyzed in terms of the following categories: a) guilt for abandoning family and friends; b) guilt for the relationship with the dependent person; and c) guilt for placing the relative in a nursing home. To validate the findings, data sources, methodological techniques, and researchers’ disciplines were all triangulated. Results indicated that women report more guilt than men for abandoning family and friends, and because of their relationship with the dependent person. However, with respect to nursing home placement, no difference was observed as a function of gender. The high incidence of caregiver guilt needs to be addressed by health professionals to avoid the emergence of other mental health issues.