Atrial fibrillation (AF) is a common arrhythmia associated with increased mortality and morbidity. Different studies have shown no significant difference between rhythm and rate control strategies in terms of mortality. Moreover, the use of antiarrhythmic drugs is afflicted by cardiac and extracardiac toxicity and related costs of hospitalization. Nevertheless, some patients require a rhythm–control strategy and new anti-AF agents are being sought. Only few novel agents showed promising results in term of efficacy and safety. Dronedarone and vernakalant are two of these compounds, respectively introduced for the chronic and acute rhythm control of AF. This article will review pharmacology and clinical evidence on the use of dronedarone and vernakalant and will mention currently investigated new antiarrhythmic drugs.