Clinical and experimental use of positron emission tomography (PET) is expanding and allows quantitative assessment of brain tumor's pathophysiology and biochemistry. PET therefore provides different biochemical and molecular information about primary brain tumors when compared to histological methods or neuroradiological studies. Common clinical indications for PET contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by PET reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by PET could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as PET represents a novel technology for molecular imaging assays of metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. PET probes and drugs are being developed together as molecular probes to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging by PET helps to close the gap between in vitro to in vivo integrative biology of disease.