The ability of cancer cells to invade, metastasize, and form distant colonies, is one of the key characteristics that confers lethality to cancer. Metastatic cancer cells typically become refractory to treatment. The metastatic cascade is a multi-step process that is governed by events within the cancer cell, the tumor microenvironment, and the distant environments that are invaded and colonized by the cancer cells. Noninvasive imaging techniques are facilitating a close examination of the stepwise journey of the cancer cell from the primary tumor to the distant metastatic site. Here we have discussed the metastatic process, and how molecular and functional imaging of cancer are providing new insights into the metastatic cascade that can be exploited for treatment of metastatic disease.