Liver transplantation (LT), the only cure for end-stage liver disease, is a lifesaving, costly, and limited resource. LT recipients (LTRs) are aging with an increasing burden of medical comorbidities. Patient and graft survival rates exceed 70% at 5 years; however, patient-centered health outcomes beyond survival have received relatively little attention. LTRs must have strong self-management skills to navigate health systems, adhere to clinical monitoring, and take complex, multidrug regimens. All of these tasks require formidable cognitive abilities for active learning and problem solving. Yet, LTRs are at higher risk for impaired cognition as a result of the high prevalence of pretransplant hepatic encephalopathy, multiple chronic conditions, alcohol use, physical frailty, sarcopenia, and older age. Cognitive impairment after transplant may persist and has been causally linked to poor self-management skills, worse physical function, and inferior health outcomes in other health care settings, yet its impact after LT is largely unknown. There is a need to study potentially modifiable, posttransplant targets including caregiver support, physical activity, sleep, and treatment adherence to inform future health system responses to promote the long-term health and well-being of LTRs. Prospective, longitudinal data collection that encompasses key sociodemographic, cognitive–behavioral, psychosocial, and medical factors is needed to improve risk prediction and better inform patient and caregiver expectations. Interventions with proactive monitoring, reducing medical complexity, and improved care coordination can be tailored to optimize posttransplant care. We propose a research agenda focused on understudied, potentially modifiable risk factors to improve the long-term health of LTRs. Our conceptual model accounts for cognitive function, caregiver and patient self-management skills, health behaviors, and patient-centered outcomes beyond mortality. We propose actionable health-system, patient, and caregiver-directed interventions to fill knowledge gaps and improve outcomes.