Postoperative atrial fibrillation (POAF) is a major complication after cardiac surgery which can lead to high rates of morbidity and mortality, an enhanced length of hospital stay, and an increased cost of care. POAF is postulated to be a multifactorial phenomenon; however, some major pathogeneses have been proposed, including inflammatory pathways, oxidative stress, and autonomic dysfunction. Genetic studies also showed that inflammatory pathways, beta-1 adrenoreceptor variants, G protein-coupled receptor kinase 5 gene variants, and non-coding single-nucleotide polymorphisms in the 4q25 chromosomal locus are involved in this phenomenon. Moreover, several predisposing factors lead to the development of POAF, consisting of pre-, intra-, and postoperative contributors. The main predisposing factors comprise age, prior history of major cardiovascular risk factors, and ischemia-reperfusion injury during surgery. The management of POAF is based on the usual therapies used for non-surgical AF, including medications for either rate control or rhythm control in hemodynamically unstable patients. The perioperative administration of β-blockers and some antiarrhythmic agents has been recommended in major international guidelines. In addition, upstream therapies consisting of colchicine, magnesium, statins, and antioxidants have attenuated the incidence of POAF; however, some uncomfortable side effects developed in large randomized trials. The use of anticoagulation has also resulted in less mortality in patients with POAF at higher risk of thromboembolic events. Despite these recommendations, the actual regimen for the prevention of POAF remains controversial. In this review, we highlight the pathogenesis, predisposing factors, and potential therapeutic options for the management of patients at risk for or with POAF following cardiac surgery.