Serotonin (5-HT) is a neurotransmitter that has important functions such as the physiological regulation of hemostasis, blood clotting, bone metabolism, cardiovascular growth, contractile activity and gastrointestinal motility, renal function, and stress and sexual behavior, among others. In this review, we consider the potential of 5-HT to contribute to the development of various pathological conditions, including metabolic, vascular, and nervous disorders in horses. The values of 5-HT in circulation are modified under common pathological conditions. Thus, laminitis, endotoxemia, surgical cramps, recurrent airway obstruction, Cushing's syndrome, central fatigue, and certain behavioral alterations such as stereotypes and other acute or chronic conditions can cause increased levels of 5-HT.