Currently, there is an increasing interest in the oncological applications of FDG-PET beyond staging. This thesis focused on the utilization of FDG-PET as an imaging biomarker. Four diagnostic challenges on this topic were subject for investigation: the understanding of the underlying mechanisms of FDG accumulation, characterization of lesions, definition of high-risk populations and prediction of treatment outcome with FDG-PET. These topics were studied in three types of cancer: non-small-cell lung cancer (NSCLC), colorectal cancer and cancer of the head- and neck area.