High-resolution cross-sectional imaging improved dramatically the diagnosis and therapy management of oncological patients, although several questions remained open, primarily concerning the exact initial staging, the differential diagnosis of recurrent tumors, and therapy management. Positron emission tomography (PET) is a quantitative, functional imaging modality from the field of nuclear medicine which has the potential to yield physiological information. The diagnosis of tumors with PET is based on the increased regional glucose metabolism. Furthermore, PET can serve as a valuable tool for monitoring therapeutic effects. The most common tracer used for oncological studies is F-18-deoxyglucose (FDG), a glucose analog. FDG-PET has been evaluated in different tumor types such as colorectal cancer, malignant lymphomas, melanomas, soft-tissue sarcomas, and lung tumors for both the diagnosis of primary tumors and recurrent lesions. The sensitivity of PET-FDG studies exceeds 85%, dependent on tumor type, size, and location. The diagnosis of viable tumor tissue following chemotherapy is another application of PET. A limitation of FDG-PET studies is false positive results, e.g., due to inflammation. This problem may be overcome by the use of multitracer studies and/or labeled amino acids. Different procedures can be used to evaluate therapeutic effects. FDG follow-up studies are used to assess early effects and to predict long-term response. Pharmacokinetic studies of labeled therapeutic agents such as F-18-fluorouracil or C-11-ethanol provide exclusively quantitative data about transport and elimination of a drug. PET with labeled cytostatic drugs permits a prognosis prior to onset of chemotherapy. This procedure is recommended for monochemotherapy. In patients receiving polychemotherapy, the evaluation of different resistance mechanisms is needed and new approaches using suitable substrates, e.g., for the P-glycoprotein, are being developed or are already in use for scientific purposes.