Several mechanisms may influence the enhanced glucose uptake in cancer cells, including upregulation of glucose transporters, increase in the hexokinase activity and the protein kinase B, also called Akt, which appears to play key role in the control of glucose metabolism together with proteins which are involved in the signal cascade pathway, such as the mammalian target of rapamycin (mTOR). It has been demonstrated in patients with gastrointestinal stromal tumors (GIST) and other sarcomas who received treatment with imatinib that PET with 18F-FDG is appropriate for treatment monitoring. Data suggest that 18F-FDG monitoring may be used for monitoring not only imatinib but also other kinase inhibitors. A 36-year-old female patient with metastasized desmoplastic small round cells tumor after a broad surgical resection of the tumor area and due to related enzyme findings, was treated with the mTOR-inhibitor everolimus (Certican, Novartis, Basel, Switzerland) at an initial dose of 3 x 0.5 mg per day targeting at a blood level of >11 ng/ml. A baseline 18F-FDG-PET demonstrated an enhanced FDG uptake in three large liver metastases and in another metastatic lesion in the pelvic area. A dynamic 18F-FDG-PET study performed six weeks later, demonstrated non-response to the mTOR-inhibitor. Despite the antiproliferative activity of mTOR-inhibitors in experimental model systems, its antitumor activity in patients may be limited. In conclusion, 18F-FDG-PET seems to be a promising method for monitoring the therapeutic effect of mTOR-inhibitors.