Serotonin (5-HT) has been recognized for decades as an important signaling molecule in the gut, but it is still revealing its secrets. We continue to discover novel gastrointestinal (GI) functions of 5-HT, as well as actions of gut-derived 5-HT outside of the gut, and we are learning how 5-HT signaling is altered in GI disorders. Furthermore, new therapeutic targets related to 5-HT signaling are being identified that can hopefully be exploited to alleviate the symptoms of functional GI disorders. Conventional functions of 5-HT in the gut involving intrinsic reflexes include stimulation of propulsive and segmentation motility patterns, epithelial secretion, and vasodilation. Activation of extrinsic vagal and spinal afferent fibers results in slowed gastric emptying, pancreatic secretion, satiation, pain and discomfort, as well as nausea and vomiting. Within the gut, 5-HT also exerts non-conventional actions that include serving as a pro-inflammatory signaling molecule and as a trophic factor to promote the development and maintenance of neurons and interstitial cells of Cajal. Platelet 5-HT, which comes from the gut, can promote hemostasis, influence bone development, and contribute to allergic airway inflammation. 5-HT3 receptor antagonists and 5-HT4 receptor agonists have been used to treat functional disorders with diarrhea or constipation, respectively. More recently, the synthetic enzyme, tryptophan hydroxylase has been targeted, and there are recent findings suggesting that epithelial 5-HT4 receptors could be targeted to provide a safe and effective treatment for constipation. Here we provide an overview of these serotonergic actions and treatment strategies.