The 14th International Headache Congress was held in Philadelphia in September 2009. During the Congress, many important basic, translational, and patient-oriented research studies were presented. In this and an accompanying manuscript, the work that has been deemed to be among the most innovative and significant is summarized. This manuscript discusses the best clinical research, while the accompanying manuscript summarizes the top basic science research. Here, we provide background and summarize Congress presentations on novel agents for migraine treatment, botulinum toxin therapy for chronic migraine, new methods for administration of headache medications, and nerve stimulation for the treatment of medically refractory headaches.