Atrial fibrillation (AF) is the most common form of tachyarrhythmia and carries a significant risk of serious thromboembolic complications. Anticoagulation is used for long-term thromboprophylaxis and for short-term management in a number of clinical situations, among which is the medical or electrical cardioversion of AF to sinus rhythm. Current guidelines recommend prompt cardioversion with heparin cover for AF of <48 h duration, and several weeks of warfarin therapy prior to cardioversion when the duration of disease is longer. Recent animal and human studies, however, have shown that swifter cardioversion is likely to be more successful in achieving sinus rhythm and in reducing the risk of recurrence of AF. Other observations have demonstrated that thrombi can develop within a few hours of the development of AF. These considerations suggest that cardioversion should be carried out as early as possible in all cases, and that the most sensitive means of detecting atrial thrombi, currently transesophageal echocardiography (TEE), should be used to screen all patients prior to cardioversion. Within this context, there is growing interest in the use of low-molecular-weight heparin (LMWH) as an anticoagulant therapy in AF. Compared with unfractionated heparin, LMWH therapy does not involve prolonged intravenous administration, hospitalization, or laboratory monitoring; LMWH therefore has the potential to greatly simplify anticoagulation therapy for AF, especially pericardioversion. Recent studies have demonstrated that LMWH can be used safely and effectively in place of unfractionated heparin for acute treatment at the onset of AF and during early cardioversion. For example, in patients with AF, a strategy of immediate administration of dalteparin (100 IU/kg s.c. twice daily) continued for 11 days, combined with early TEE and immediate cardioversion in patients with no thrombus, resulted in sinus rhythm in 74% of patients after a median of 7 days. Low-molecular-weight heparin therapy may also find a role perioperatively and in selected patients, notably those with warfarin intolerance, as a replacement for warfarin following cardioversion. Controlled clinical studies are still required, however, to establish a firm, evidence-based foundation for the use of LMWHs in AF.