Although introduction of hybrid positron emission tomography/computed tomography (PET/CT) scanners represents an important development in field of radiology, the alliance of functional imaging with structural imaging has raised many controversial issues. The present review describes some of the important issues in hybrid PET/CT such as specific indications, protocols that deliver diagnostic quality CT scans while ensuring radiation dose associated with hybrid PET/CT examination are minimized, and the feasibility, desirability, and timing of oral and intravenous contrast administration. The issues of clinical indications for hybrid PET/CT versus PET alone will be discussed as well as the role of the CT component (ie, for diagnosis or transmission source alone) are discussed. The logistics of hybrid PET/CT scan interpretation, including the roles of radiologists and nuclear medicine physicians, will be discussed. This review describes the pertinent medical literature and discusses our experience with suitable examples.