The importance of computed tomography (CT) as one of the leading radiology technologies applied in the field of biomedical imaging escalated the development of nanoparticles as the next generation CT contrast agents. Nanoparticles are expected to play a major role in the future of medical diagnostics due to their many advantages over the conventional contrast agents, such as prolonged blood circulation time, controlled biological clearance pathways and specific molecular targeting capabilities. This paper will describe the basic design principles of nanoparticle-based CT contrast agents and review the state-of-the-art developments and clinical applications of blood pool, passive and active targeting CT contrast agents.