While it is widely recognized that poor diet is a leading cause of many chronic diseases, the U.S. health care system has done relatively little to systematically improve diets within the U.S. population. The field of Food Is Medicine (FIM) has worked to bridge this gap by connecting at-risk patients in the health care system with services that increase access to healthy food to prevent, manage, or treat specific clinical conditions. Concern about unmet social needs that significantly affect health outcomes and cause health inequities has only heightened emphasis on the field. In this context, the American Heart Association’s Health Care by Food (HCXF) initiative envisions a future in which food therapy is used and reimbursed alongside or instead of traditional drug therapy to prevent and treat many diet-related conditions. The HCXF initiative aims to build the evidence needed to show the clinical effectiveness and cost-effectiveness of FIM interventions. The authors surveyed existing research to identify current evidence as well as evidence gaps across the field. Suboptimal engagement surfaced as a major challenge — unsurprisingly, given that shifting diet is a significant behavior change. Existing FIM programs that focus on providing free or subsidized food to people suffering from chronic conditions and food or nutrition insecurity have found that a significant number of vouchers are often left unused. Because of this, the HCXF initiative emphasizes human-centered design and behavioral science. In addition, the authors have established a cooperative studies framework intended to enhance the ability of research teams to conduct rigorous studies. Research teams receive review and ongoing support from human-centered designers and behavioral scientists, as well as experts in statistics, cost-effectiveness, and community engagement and implementation science.