The prevalence and persistence of atrial fibrillation (AF) and the relative inefficacy of the currently available pharmacotherapy requires development of new treatment strategies. Recent findings have suggested a mechanistic link between inflammatory processes and the development of AF. Epidemiological studies have shown an association between C-reactive protein and both the presence of AF and the risk of developing future AF. In case-control studies, C-reactive protein is significantly elevated in AF patients and is associated with successful cardioversion. Moreover, C-reactive protein elevation is more pronounced in patients with persistent AF than in those with paroxysmal AF. Furthermore, treatment with glucocorticoids, statins, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers seems to reduce recurrence of AF. Part of this anti-arrhythmic effect may be through anti-inflammatory activity. This article reviews what is known about inflammation in genesis and perpetuation of AF, the putative underlying mechanisms, and possible therapeutic implications for the inhibition of inflammation as an evolving treatment modality for AF.