Some of the most exciting advances in molecular-functional imaging of cancer are occurring at the interface between chemistry and imaging. Several of these advances have occurred through the development of novel imaging probes that report on molecular pathways, the tumor micro-environment and the response of tumors to treatment; as well as through novel image-guided platforms such as nanoparticles and nanovesicles that deliver therapeutic agents against specific targets and pathways. Cancer cells have a remarkable ability to evade destruction despite the armamentarium of drugs currently available. While these drugs can destroy cancer cells, normal tissue toxicity is a major limiting factor, a problem further compounded by poor drug delivery. One major challenge for chemistry continues to be to eliminate cancer cells without damaging normal tissues. Here we have selected examples of MRI and optical imaging, to demonstrate how integrating imaging with novel probes can facilitate the successful treatment of this multifaceted disease.