This chapter presents discussion on 5-hydroxytryptamine (5-HT) agonists and antagonists. It is widely distributed in plants and animals (banana, pineapple, wasp, scorpion sting). 5-HT is stored in enterochromaffin cells of gastrointestinal (GI) mucosa. 5-HT receptors, 5-HT agonists, 5-HT antagonists, ergot alkaloids, and drug treatment of migraine are the other topics which are also covered thoroughly in this chapter.