Complex caregiving issues occur in multigenerational families carrying the fragile X mutation and premutation. The same family members may care for children or siblings with fragile X syndrome (FXS) and for elderly parents with fragile X-associated tremor/ataxia syndrome (FXTAS). Family caregivers experience anxiety, depression, neglect of personal health care needs, employment difficulties, and loss of social support, leading to isolation and further psychiatric consequences. There is growing awareness of caregiver burden with regard to parents of children with FXS, but much less is known about the needs of informal caregivers of patients with FXTAS. In this paper, we review the available literature to date and provide suggestions for further exploration of caregivers’ needs. Evidence-based strategies to address these needs are included. Many more research studies exploring caregiver burden in multigenerational fragile X families are needed, as well as studies aimed at investigating interventions and their impact on burden reduction.