Background: Cardioplegic solutions are widely used for myocardium protection during cardiac surgery. Custodiol cardioplegia has begun to gain popularity in recent years in cardiac surgery because of its administration, in a single dose, providing protection for 1.5 - 2 hours. Purpose: of this study was to review the current literature related to the Custodiol efficacy on the protection of myocardium in cardiac surgery. Methodology: The methodology followed included searching for research data, which was collected through electronic databases PubMed, Google Scholar, Medline, Research Gate. Results : A large number of papers have studied the effect of Custodiol cardioplegia, which has been used today in a large set of cardiac surgery for cardiac arrest, whereas its use has recently been extended to minimally invasive heart surgery and is also used to maintain heart transplants. Custodiol is a safe and effective cardioplegic solution that can provide adequate protection for the myocardium over a period of at least 2 hours, as assessed by cardiac biomarkers and other postoperative effects such as aortic cross-clamp time, blood transfusion requirements, inotropic support and mortality. In this context, Custodiol is often preferred in more complex cardiac surgery to avoid disruption of the surgical operation. In minimal invasive cardiac surgery, the use of Custodiol to avoid repeated infusions of other cardioplegic solutions may reduce the risk of poor perfusion due to atrial retractor off and enhance the surgeon's comfort during the procedure. Conclusions : More research is needed to confirm and extend the above findings in well designed and large randomized trials. The effect of a modified solution (Custodiol-N), as well as the pharmacological modification of Custodiol with the addition of pinacidol and lidocaine, is currently investigated in animal models to enhance induced cardiac protection.