Objective: To establish the evidence base for animal-assisted interventions, and specifically, hippotherapy and other interventions involving horses, in the context of improving biological, physical, psychological and social functioning, and outcomes in humans. Method: A review of systematic reviews (an umbrella review) was carried out using a modified Joanna Briggs Institute methodology and following PRISMA guidelines. Inclusion criteria were any interventions that included a live horse, for humans of any age and for any therapeutic purpose. Service and assistance horses and people who were incarcerated were excluded. Systematic reviews with a clearly articulated and comprehensive search strategy, with evidence of critical appraisal, both qualitative and quantitative and mixed methods, and in English were considered. Results: Of 19 systematic reviews considered eligible for inclusion, 13 were included in this umbrella review. These 13 systematic reviews covered 79 individual studies of equine-assisted interventions, including primarily hippotherapy and therapeutic horse riding. Participants included children with cerebral palsy, children and adolescents with autism spectrum disorder, adults with multiple sclerosis, elderly people, adults post-stroke, people with spinal cord injury, adults with serious mental illness, adults with balance problems, people with brain disorders, breast cancer survivors, and obese women. Conclusions: The evidence for equine-assisted interventions for adults and children across a range of conditions and presentations is equivocal. The current evidence base is marred by multiple methodological weaknesses and thus, therapeutic interventions that include a horse cannot be asserted as best practice at this time. Rigorous research is indicated to determine the utility of equine-assisted interventions.