Recent innovations in transplantation, such as tailored immunosuppressive regimens, thorough preoperative psychosocial evaluations, and the emergence of non-invasive graft monitoring strategies through novel molecular technologies, have led to increased longevity and quality of life of the recipients. However, heart transplant (HTx) recipients face numerous challenges in the post-operative setting. In particular, patients are expected to adhere to a complex multi-drug medication regimen, including maintenance immunosuppression to prevent rejection, as well as prophylactic medications for infectious, coronary vasculopathy, and general health protection. In this chapter, we discuss adherence with medical and lifestyle habits post-HTx, its association with outcomes, and outline current interventional strategies to improve adherence in HTx recipients.