Eletriptan is a new selective serotonin agonist approved for the treatment of acute migraine headaches. To review the pharmacologic, pharmacodynamic, pharmacokinetic, safety, and clinical efficacy data for eletriptan, we searched the literature in PubMed/MEDLINE, EMBASE, International Pharmaceutical Abstracts, and Science Direct databases to gather all published reports from January 1996-October 2004. All English-language reports (abstract or full trial reports) about the pharmacology, pharmacokinetics, clinical efficacy, and safety of eletriptan were reviewed. Eletriptan's pharmacokinetic and pharmacodynamic parameters translate into a favorable safety and efficacy profile. The drug is rapidly absorbed when administered orally, has good bioavailability and central nervous system penetration due to its lipophilicity, and has a long half-life, which contributes to its ability to prevent recurrent headaches. Compared with other serotonin agonists, eletriptan has a longer duration of action and greater lipophilicity. Eletriptan is metabolized through the cytochrome P450 3A4 system; therefore, it does have the potential for clinically significant drug interactions. In clinical trials, eletriptan demonstrated efficacy superior to that of placebo and similar or superior efficacy to that of other serotonin agonists, with limited adverse effects. With clinical use, headache and pain-free responses and headache recurrence rates were similar to those of other serotonin agonists, but the agent is superior to ergotamine tartrate-caffeine. Based on pharmaco-economic data, eletriptan is more cost-effective than other agents in its class. Eletriptan is a safe and cost-effective option for the treatment of migraine headaches.