Positron emission tomography-computed tomography (PET-CT)-based radiation therapy (RT) treatment planning has become widely available in many RT practices. This broad acceptance has been facilitated by the RT specific features which are now commonly available on practically all modern PET-CT scanners. The quality and usability of PET-CT studies for RT treatment planning purposes strongly depends on patient positioning and immobilization during image acquisition. A well-developed clinical process and understanding of special needs for this type of imaging is crucial for successful use of PET-CT in radiation therapy planning and treatment. This article describes some of the important considerations in this process and provides several observations based on clinical experience with use of PET-CT imaging in radiation therapy planning and treatment. The use of fiducial markers in this process is also discussed.