Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with a series of adverse complications that cause so-called AF socioeconomic burden. Apart from the classical risk factors, it seems to be novel factors that increase the risk of AF and AF-related stroke. Recently, more and more evidence has well documented the close relationships between homocysteine (Hcy) and AF. As a well-known marker for pro-oxidation and pro-inflammation, Hcy plays an important role in a number of vascular diseases having strong association with AF. This review will discuss the expression of Hcy and its association with ischemic stroke in AF patients especially for elderly patients, and the role and clinical implications of Hcy in the thromboembolic events and rhythm outcome in AF patients. The possible mechanisms linking elevated Hcy and cardiovascular events in AF patients will also be addressed, including oxidative stress, inflammatory response, atrial remodeling, etc.