Chronic constipation is a frequently reported medical disorder that reduces patients' quality of life and imposes a significant economic burden on the health care system. Symptoms of constipation are diverse and include infrequent bowel movements, hard stool, straining at stool, sensations of anorectal obstruction and feelings of incomplete evacuation. Patients with chronic constipation can be categorized into one of three main groups based on their underlying pathophysiology: normal transit constipation; colonic inertia; and pelvic floor dyssynergia. Specialized tests (i.e., anorectal manometry, radio-opaque marker study) may be required in some patients to help distinguish the different subtypes of constipation and to guide appropriate therapy. Although the underlying mechanism of constipation differs among patients, serotonin (5-hydroxytryptamine (5-HT)) appears to have an important role in colonic motility in some patients. Previous research has demonstrated that stimulation of 5-HT4 receptors improves symptoms of chronic constipation in some patients. Prucalopride, a selective 5-HT4 agonist, relieved symptoms of constipation in phase II and phase III clinical trials. In this monograph, we review the pharmacology, mechanism of action, efficacy and safety of the selective 5-HT4 agonist prucalopride in patients with chronic constipation.