Background Caregivers of people with Multiple Sclerosis are required to provide ongoing assistance especially during the advanced stages of the disease. They have to manage interventions and assume responsibilities which significantly impact both their personal quality of life and family’s dynamics. Objective A qualitative phenomenological study was carried out to understand the experience of burden in caregivers and their resources to manage it. The study also explores how healthcare services involved in the Multiple Sclerosis Clinical Pathway respond to the needs of well-being of patients and family members. Methods 17 caregivers were involved in focus groups and in semi-structured individual interviews. Results Fatigue is experienced by all respondents and it starts when physical disabilities increase or when people become aware of them. Many caregivers declare that they refer to intrinsic (love towards their relatives, patience and dedication) or extrinsic (family members, hobbies) resources to cope with the burden of assistance. Patient associations and the Multiple Sclerosis Clinical Pathway play a significant role in supporting caregivers. Conclusions Fatigue, loneliness, and isolation are experienced by caregivers and strongly affect their quality of life and health status. The study highlights caregivers’ need to reconcile working times with care times, to give more space to self-care and to have moments to share their experiences with someone else. These needs should be at the core of health policies in order to avoid physical and emotional breakdowns which could lead to the rupture of the relational balance on which home care is based.