In the past, enormous public and private investments have been made to reduce cancer incidence and mortality. Despite some improvements over the last 10 years, the overall outcome of the "war on cancer" has been disappointing. Among the reasons for this limited success is our inability to determine, whether the therapeutic target is present, and whether the target is reached by the drug. A further important issue is our limited ability to correctly assess response to treatment early after start of therapy which would allow for more individualized treatment approaches. PET and PET/CT with the glucose analogue 2'-[(18)F]-fluoro-2'-deoxy-D-glucose (FDG) are increasingly used to assess response to therapy in patients, and a converging large body of evidence is emerging that suggests that changes in glucose utilization during therapy can be used to predict clinical outcome. In this article we provide an overview of the utility of (18)F-FDG PET/CT imaging for early monitoring of cancer therapy and address current and future challenges for its more widespread adoption. First, we discuss general requirements that any imaging modality must meet to provide valid and valuable treatment response assessment. We will then review the strengths and limitations of CT (RECIST) and PET based response criteria. Finally, we will examine the role of FDG-PET/(CT) imaging for response assessments in solid tumors.