As personalized medicine becomes a reality, there is a need for specific imaging agents that reflect molecular characteristics of a cancer. Fluorodeoxyglucose is an important advance because of its sensitivity. Newer molecular imaging probes offer higher specificity and are categorized as: radiolabeled biomimetics; antibody–antibody fragments and drug–drug-like compounds. Biomimetics have high sensitivity but tend to be less specific as they often engage natural transporters and metabolic pathways. Antibodies and their fragments are specific but may be limited by slow clearance. Labeled drugs and drug-like compounds offer good specificity but may be limited in sensitivity. There are numerous challenges facing molecular imaging related to their complexity. Additionally, fear of ionizing radiation and regulatory constraints have somewhat inhibited clinical translation. However, there is reason for optimism due to economies of scale and a changing health care system, which places a premium on diagnostic accuracy. Although molecular imaging is not likely to become mainstream in the near future, its long-term prospects for doing so are excellent.