Fever of unknown origin (FUO) or pyrexia of unknown origin (PUO) is a real medical issue at times. Modern investigations can help in diagnosing but in some rare cases, it remains a medical challenge. Patients and clinicians are worried about unexplained fevers. Causes of most of the fevers is identified and approach to diagnosis in such cases is usually related to history, physical examination and basic laboratory clues. The correct approach in such cases is to follow clues and start with the least invasive evaluation. This will help in avoiding unnecessary harm and cost to the patient. Miscellaneous conditions also cause FUO.