There is currently no consensus regarding the dose or duration of rabbit antithymocyte globulin (rATG) induction in different types of heart transplant patients, or the timing and intensity of initial calcineurin inhibitor (CNI) therapy in rATG-treated individuals. Based on limited data and personal experience, the authors propose an approach to rATG dosing and initial CNI administration. Usually rATG is initiated immediately after exclusion of primary graft failure, although intraoperative initiation may be appropriate in specific cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that range according to immunologic risk and adjusted according to immune monitoring. Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory support. The timing of CNI introduction is dictated by renal recovery, varying between day 3 and day 0 after heart transplantation, and the initial target exposure is influenced by immunological risk and presence of infection. Rabbit antithymocyte globulin and CNI dosing should not overlap except in high-risk cases. There is a clear need for more studies to define the optimal dosing regimens for rATG and early CNI exposure according to risk profile in heart transplantation.