Thirty percent of persons with multiple sclerosis (pwMS) require caregiving owing to their disability, and 80% of care to pwMS is provided by informal unpaid caregivers. The average caregiver is male, in a spousal/partner relationship with the pwMS, and provides more than 4 hours per day of care for many years. The physical, emotional, and time-intensive nature of caregiving for pwMS frequently impairs the caregiver’s own physical and emotional health. Rehabilitation medicine professionals should be aware of the high risk of caregiver burden. Assessment of caregiver needs and appropriate intervention will help minimize the burden on caregivers.