The design of new generation drugs acting as 5-HT1 receptor agonists, in the field of acute treatment of migraine, is still very active. The reason is the need for safer medicines with improved response rates and a reduced rate of headache recurrence. This review focuses on the different classes of drugs, which have been classified based on the target upon which they act rather than upon structural characteristics. Short SAR studies are reported for each series with a detailed pharmacological profile for the most interesting compounds.