More than 250,000 patients undergo cardiac surgery every year. Although advances in surgical techniques have reduced the peri-operative morbidity and mortality in these patients, atrial fibrillation persists to commonly occur following these surgeries. Traditional therapies have reduced their occurrence; however there are still a significant number of patients who develop this complication. Newer and non-conventional medications are being studied to reduce this cardiac arrhythmia. This review will elaborate on the patho-physiology, and prevention of this arrhythmia. We also aim to summarize recent investigated and patented medications which may result in more effective strategies for prophylaxis against this cardiac arrhythmia.