Background and objectives: Migraine is a highly prevalent neurological disorder with multiple mechanisms. Targeting a single mechanism has been found only partially effective for treating individual attacks. Recently, the role of combining agents for the acute migraine treatment has gained attention and the combination of a triptan plus a nonsteroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This article focuses on the review of available literature for treating migraine attacks with two or more agents, related patents as well as analyzes the characteristics of the recently approved fixed combination sumatriptan-naproxen. Methods: The following terms migraine, acute treatment, sumatriptan, naproxen and combination were searched on MEDLINE. In addition, abstracts presented in the major meetings carried out by the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. Results: Although most of the few studies encountered were not controlled, there is a clear trend for the better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50mg and 85mg) with 500mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the isolated use of each agent. The differences in the endpoints of 24-hour pain relief response as well as pain-free and pain-relief parameters at 2-hour time-points are the clearest efficacy measures. Tolerability was not different between the two studied drugs. Conclusions: Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over the monotherapy. Recently, issued FDA approval for marketing the combination (sumatriptan 50mg-naproxen 500mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.