Osteomyelitis in the diabetic foot can be difficult to diagnose and has serious consequences. Although 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET) was traditionally used in oncology, it is emerging as a useful method in inflammatory and infectious entities. In this chapter, original research articles, meta-analyses, and reviews on the performance of FDG PET in diagnosing osteomyelitis in the diabetic foot will be discussed. In addition, PET available data in comparison to different imaging methods, different analysis methods, and impact of other co-existing conditions such as hyperglycemia, and long-term antibiotic treatment on the performance of FDG PET will be reviewed. Studies published in the last two decades showed variable performance of FDG PET in the assessment of diabetic foot infection with a relatively high specificity (67-93%) but a wide range of sensitivity (29-100%). More recent studies showed better sensitivity, probably due to improved imaging technology and analysis methods and use of hybrid imaging with positron emission tomography/ computed tomography (PET/CT). FDG PET/CT has several advantages compared to other anatomical and functional imaging methods, including short acquisition time, high resolution, low radiation dose, and better tolerability. Further research is required to establish its role in the clinical practice.