Society and medical practice have been restructured dramatically to avoid further spread of the COVID-19 virus; telehealth/telemedicine, mask wearing, and nationwide social distancing practices have become widespread. However, we still face unprecedented challenges in fields where patients require frequent and active follow-up visits for monitoring, including that of solid-organ transplant, and in particular, heart transplant. Adherence to immunosuppression remains a unique challenge in heart transplantation, especially during the COVID-19 pandemic. Failure to adhere to immunosuppression can have disastrous consequences, including graft rejection and death. In this article, we discuss challenges related to adherence to immunosuppression medications among heart transplant recipients, as well as opportunities to leverage digital approaches and interventions to monitor and optimize adherence behavior and health outcomes in this population.