Medical imaging technologies allow for the rapid diagnosis and evaluation of a wide range of pathologies. In order to increase their sensitivity and utility, many imaging technologies such as CT and MRI rely on intravenously administered contrast agents. While the current generation of contrast agents has enabled rapid diagnosis, they still suffer from many undesirable drawbacks including a lack of tissue specificity and systemic toxicity issues. Through advances made in nanotechnology and materials science, researchers are now creating a new generation of contrast agents that overcome many of these challenges, and are capable of providing more sensitive and specific information. In this review, we summarize the main classes of nanotechnology-based contrast agents for each of the major imaging technologies, and highlight progress in their development as well as the challenges to be addressed. We also review the relevant biological interactions that determine the in vivo fate of these contrast agents, and describe major themes in medical nanotechnology including stealth and targeting.