Occasionally a horse will present with fever and all the clinical signs that accompany fever including depression and loss of appetite. If this goes on for more than a few days dehydration and weight loss may occur. These nonspecific clinical signs can present as a diagnostic dilemma as there are many possible causes that range from self limiting diseases to a life threatening crisis. Fever of unknown origin (FUO) is a common dilemma facing the horse owner and veterinarian. This article outlines the assessment of cases of FUO, routine to pursue a diagnosis, and a list of possible causes each with a links to more detailed articles on the possible causes.