Molecular imaging has emerged as a powerful tool to visualize molecular events of an underlying disease, sometimes prior to its downstream manifestation. This presents a whole new paradigm disease diagnosis and monitor treatment. Nanotechnology is another rapidly growing field that offers new materials with unique physical and chemical properties that may find broad application in biomedical research. The merging of nanotechnology with molecular imaging provides a versatile platform for novel design of nano-probes that will have tremendous potential to enhance the sensitivity, specificity, and signaling capabilities of various biomarkers in human diseases. In this review, the general construct and key characteristics of nanoprobes in the context of molecular imaging are highlighted. The various designs of nanoprobes based on their targeting mechanisms, strategies for contrast enhancement, multi-modality imaging and imaging/ therapy hybrid systems are outlined along with a discussion on the current status of imaging equipment design. Additionally, the potential challenges for adapting nanoprobes for molecular imaging including toxicity, biodistribution/pharmacokinetics, and synthetic feasibility are addressed.