While much of the knowledge accumulated for COVID-19 is relevant to the general population and immunosuppressed patients alike, some of the particular characteristics of heart transplant (HTx) recipients warrant tailored approaches to patient management and to prevention and treatment. Although there are several pharmacologic therapies available for HTx recipients, it should be remembered that this is a rapidly evolving field, further emphasizing the crucial roles of transplant team in managing the patients according to the most up-to-date guidelines. Particularly important in the crystallization of a vaccination policy was to encourage vaccination as soon as vaccines became available. The impact of the accumulated data on SARS-CoV-2 will extend beyond protection from COVID-19 into the implementation of new vaccine technologies for various other infectious disease targets, improving preparedness for future health crises, and into applications for oncology, metabolic diseases, gene therapy, and gene editing. This chapter will explore the management of COVID-19 in HTx patients and vaccination strategies.