Despite a growing body of research on male caregivers, limited information is available on male caregivers of cancer survivors. Furthermore, few studies have examined the unique contribution of caregiver esteem as well as care-recipient's functional status as potential mediators of the link between gender and caregiving stress. Thus, the present study examines how the caregiver's perception of providing care to a spouse with cancer differs by gender. The proposed mediators, caregiver's esteem and care-recipient's psychosocial and physical functioning, were tested simultaneously, utilizing structural equation modeling. Results revealed that both caregiver's esteem and care-recipient's psychosocial functioning were significant mediators, but in different directions. Specifically, husband caregivers reported higher caregiver's esteem, which resulted in reporting less stress from providing care to their wife with cancer. On the other hand, when husband caregivers provided care to their wife with poorer psychosocial functioning, they reported greater stress from caregiving. Husband caregivers will benefit from programs designed to educate them to effectively assist their wife's psychosocial adjustment to cancer by reducing their stress from providing care. Copyright (C) 2006 John Wiley & Sons, Ltd.