The introduction of open-heart surgery more than 4 decades ago signaled a new era in medicine. For the 1st time, previously untreatable cardiac anomalies became amenable to surgical therapy. The use of the heart-lung machine seemed to grant the surgeon unlimited time in which to operate inside the heart. Still frustrated by poor operating conditions and the threat of air embolism, Denis Melrose introduced elective cardiac arrest in 1955. His use of a potassium citrate solution seemed to offer a safe method to effect a quiet, bloodless field. However, a few years after its inception, numerous reports began to question the safety of this approach, and the Melrose technique was abandoned in the early 1960s. Nearly 15 years elapsed before potassium-based cardioplegia regained popularity. During this period, topical hypothermia, coronary perfusion with intermittent aortic occlusion, and normothermic ischemia were evaluated and discarded. A few European investigators like Hoelscher, Bretschneider, and Kirsch had maintained their interest in chemical cardioplegia, and it was through their efforts that future researchers like Hearse and Gay spearheaded the return to potassium-based cardioplegia, which today forms the core of the cardiac surgeon's myocardial protective armamentarium and has contributed towards lowering operative mortality rates.