Fever of unknown origin (FUO) and suspected focal infection or inflammation are challenging medical problems. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with FUO and patients with suspected focal infection or inflammation. All FDG PET scans ordered because of FUO or suspected focal infection or inflammation in the last 4 years were reviewed. These results were compared with the final diagnosis. Thirty-five FDG PET scans were performed in 35 patients with FUO. A final diagnosis was established in 19 patients (54%). Of the total number of scans, 37% were clinically helpful. The positive predictive value of FDG PET in these patients was 87% and the negative predictive value was 95%. Fifty-five FDG PET scans were performed in 48 patients with suspected focal infection or inflammation. A final diagnosis was established in 38 patients (82%). Of the total number of scans, 65% were clinically helpful. The positive predictive value of FDG PET in these 55 episodes of suspected infection or inflammation was 95% and the negative predictive value was 100%. It is concluded that FDG PET appears to be a valuable imaging technique in the evaluation of FUO and suspected focal infection or inflammation. Furthermore, FDG PET could become a useful tool for evaluating the effect of treatment of infectious and inflammatory processes that cannot reliably be visualised by conventional techniques. However, to assess the additional diagnostic value of this technique, prospective studies of FDG PET as part of a structured diagnostic protocol are warranted.