When treating patients with migraine, clinicians should consider prescribing appropriate combinations of acute and preventive therapies. An effective migraine-preventive therapy should be prescribed to patients with frequent (≥2 migraines per month) or severe migraine. Topiramate has been shown to be an effective and generally well-tolerated migraine prophylaxis (preventive) therapy in adults, as demonstrated in several large, controlled trials. The most common adverse events in these trials were paresthesia, fatigue, anorexia, nausea, taste alteration, and diarrhea. Most adverse events were mild to moderate and transient in nature. Although patients should take migraine-preventive medications for approximately 2 to 3 months before evaluating effect, topiramate has shown efficacy as early as the first month of treatment. This article describes “real-world” approaches to using topiramate as a migraine-preventive therapy. Topiramate has received regulatory approval for the prophylaxis of migraine headache in adults in the United States and many other countries. The practical issues discussed in this article will enable clinicians to maximize the effectiveness while minimizing the side effects associated with this preventive agent.