The combination of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) for dual-modality imaging (PET/CT) plays a key role in the diagnosis and staging of FDG-avid malignancies. FDG uptake by the tumor cells offers an opportunity to detect cancer in organs that appear normal at anatomic imaging and to differentiate viable tumor from posttreatment effects. Quantification of FDG uptake has multiple clinical applications, including cancer diagnosis and staging. Dedicated FDG PET/CT–based visual and quantitative criteria have been developed to evaluate treatment response. Furthermore, the level of tumor FDG uptake reflects the biologic aggressiveness of the tumor, predicting the risk of metastasis and recurrence. FDG uptake can be measured with qualitative, semiquantitative, and quantitative methods. Qualitative or visual assessment of PET/CT images is the most common clinical approach for describing the level of FDG uptake. Standardized uptake value (SUV) is the most commonly used semiquantitative tool for measuring FDG uptake. SUV can be measured as maximum, mean, or peak SUV and may be normalized by using whole or lean body weight. SUV measurements provide the basis for quantitative response criteria; however, SUVs have not been widely adopted as diagnostic thresholds for discriminating malignant and benign lesions. Volumetric FDG uptake measurements such as metabolic tumor volume and total lesion glycolysis have shown substantial promise in providing accurate tumor assessment. SUV measurement and other quantification techniques can be affected by many technical, physical, and biologic factors. Familiarity with FDG uptake quantification approaches and their pitfalls is essential for clinical practice and research.