In India, half the burden of pyrexia of unknown origin (PUO) is contributed by infectious diseases with neoplastic disorders comprising another quarter and rheumatic disorders contributing about 10%. The causes of “Classical” PUO in infants differ from that in children which in turn is different from those seen commonly in adults. The incidence of infectious causes of PUO is significantly higher among infants given the fact that rheumatic and neoplastic disorders are relatively rare in this age group. Among infectious causes of PUOs in children, viral infections predominate. Osteomyelitis and urinary tract infections are frequently encountered. A thorough search should be made to identify infectious diseases endemic to the area visited, using focussed history and investigations targeted at diagnosing these conditions. Because fever of unknown origin (FUOs) are caused by such a wide variety of disorders, the diagnostic approach to the FUO patient is often extensive. Many patients with PUO undergo more than one biopsy in an effort to establish a definitive diagnosis. The diagnostic yield of CT or Ultrasonography guided biopsies in considerably higher than blind procedures. An exploratory laparotomy may also be needed if all other modalities fail in confirming the diagnosis. The emphasis when encountering such a case should be clearly on diagnosing the underlying condition rather than on empirical therapy.