This article reviews possible clinical applications of positron emission tomography (PET) in patients with CNS lymphomas. PET allows quantitative assessment of brain tumor pathophysiology and biochemistry in vivo. Therefore, it provides different information about tumors when compared to histological or neuroradiological methods. In a diagnostic setting, PET cannot differentiate between primary lymphomas of the CNS, brain secondaries, or malignant gliomas, since various brain tumors share biochemical alterations. In HIV patients with contrast-enhancing brain tumors, however, data from the literature suggest that PET with the tracer F-18 fluoro-deoxyglucose may help to discriminate neoplastic (CNS lymphoma) from inflammatory (e.g. toxoplasmosis) lesions. Assuming that tumor biochemistry is highly abnormal in the most malignant parts of tumors, PET may also assist in defining targets for stereotactic biopsy. With regard to treatment evaluation, the prediction of individual treatment response is among the most challenging clinical applications of PET. On the one hand, this could be achieved on the basis of measures like tumor perfusion, oxygen consumption, or hypoxia. On the other hand, PET tracer methods may allow to quantify the expression of gene products following gene therapy. However, in CNS lymphoma patients these topics have yet not been addressed with PET.