Positron emission tomography–computed tomography (PET-CT) using the glucose metabolism tracer 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) has become a widespread and preferred imaging modality for evaluating most cancers. Since commercial PET-CT scanners became available in 2001, there has been rapid dissemination of this hybrid imaging modality and PET-CT scanners have largely replaced stand-alone PET scanners. How PET-CT scans are performed and applied to cancer management has varied considerably, in part reflecting the varied background of the practice settings and training experience of the physicians performing and interpreting the PET-CT studies. Combined PET/CT with FDG has become the gold standard in oncologic imaging by accurately defining anatomy and function of many tumors. From April 2-4, 2008, a focus group composed of physicians and technologists from different practice settings and training backgrounds entitled “Best Practices in PET/CT Symposium” was held in Sonoma, California. The symposium focused on optimization of PET-CT protocols but also included other pertinent topics related to PET-CT imaging in oncology. This article summarizes areas of consensus reached by the group regarding many of the discussion topics. The summary consensus covered in this article is meant to provide direction for future discussions on how to improve the application of this hybrid modality to patient care.