Over the past decades, Positron Emission Tomography has opened a new field of imaging. Nowadays, this technique is being used for diagnosing, staging disease as well as for prognostic stratification and monitoring therapy. In this respect, [18F]fluorodeoxyglucose (FdGlc) is by far the most commonly used PET agent. Many factors have been identified being responsible for a high uptake of this agent in malignancy. However, additional factors such as tumour treatment may interfere with the uptake mechanism. Knowledge of all these factors is a prerequisite for an optimal interpretation of PET studies and, consequently, for a reliable judgement of tumour status. In this article, a review is given of the factors influencing FdGlc uptake and the implications for clinical studies.