Cancer is one of the major causes of mortality and morbidity in our health care system. Molecular imaging is an emerging methodology for the early detection of cancer, and the development of exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect pre-malignant lesions. This integrated imaging strategy will permit clinicians to not only localize lesions within the body, but also to visualize the expression and activity of specific molecules. This information is expected to have a major impact on diagnosis, therapy, drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, nuclear and MRI imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research.