Abstract: Objective: This systematic review examines the empirical literature in an emerging body of evidence for the effectiveness of biopsychosocial interventions involving equines across populations with chronic illness or health challenges. Method: Selected quantitative studies published in peer-reviewed journals were reviewed for inclusion; the gray literature and white papers were also explored. Population, Intervention, Comparison, and Outcome (PICO) criteria and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were applied to all studies. Fourteen full reports meeting a priori inclusion criteria were extracted from 103 studies accessed through 16 electronic databases and a hand search. Data were synthesized in relation to three research questions informing evidence-based practice. Results: No randomized clinical trials were located. Two studies provided a moderate level of evidence for effectiveness. Nine studies demonstrated statistically significant positive effects. Three studies did not find significant psychosocial effects for the target group, although one found significant positive effects for the comparison group. Conclusion: In the aggregate, the evidence is promising in support of the effectiveness of complementary and adjunct interventions employing equines in the treatment of health challenges. Future studies are needed that utilize rigorous and creative designs, especially longitudinal studies and comparisons with established effective treatments.