“Depolarized arrest”, induced by hyperkalemic (moderately increased extracellular potassium) cardioplegia is the gold standard to achieve elective temporary cardiac arrest in cardiac surgery. Hyperkalemic cardioplegic solutions provide good myocardial protection, which is relatively safe, and easily and rapidly reversible. However, this technique has detrimental effects associated with ionic imbalance involving sodium and calcium overload of the cardiac cell induced by depolarization of the cell membrane. Hence, the development of an improved cardioplegic solution that enhances myocardial protection is anticipated as an alternative to hyperkalemic cardioplegia. In this review, we assess the suitability and clinical potential of cardioplegic agents to induce “non-depolarized arrest” from the viewpoint of rapid cardiac arrest, myocardial protection, reversibility, and toxicity. “Magnesium cardioplegia” and “esmolol cardioplegia” have been shown to exert superior protection with comparable safety profiles to that of hyperkalemic cardioplegia. These alternative techniques require further examination and investigation to challenge the traditional view that hyperkalemic arrest is best. Endogenous cardioprotective strategies, termed “ischemic preconditioning” and “ischemic postconditioning”, may have a role in cardiac surgery to provide additional protection. The elective nature of cardiac surgery, with the known onset of ischemia and reperfusion, lends it to the potential of these strategies. However, the benefit of preconditioning and postconditioning during cardiac surgery is controversial, particularly in the context of cardioplegia. The clinical application of these strategies is unlikely to become routine during cardiac surgery because of the necessity for repeated aortic crossclamping with consequent potential for embolic events, but offers considerable potential especially if “pharmacological” preconditioning and postconditioning could be established.