Metastasis is the multistep process by which cancer cells target and colonize secondary organs. Cancer cells locally invade by breaching extracellular matrix barriers, gaining access to vasculature, and extravasating into the distant organs. This is followed by their growth in the new environment, culminating in metastatic colonization. Lung, liver, brain and bone are common sites of metastasis for many human cancers. There is a considerable debate concerning the identity of rate limiting steps in metastasis, thus modeling individual steps, and gaining molecular understanding of this process presents significant challenges. We will discuss the recent technologies and genetic mouse models which are emerging to meet these challenges.