Despite advances in surgical and clinical management, metastatic disease, notably to the lungs, liver, bone, and brain is the most common cause of death from breast cancer. Two basic principles govern the process of metastasis. First, that the tumors are heterogeneous populations of cells, and second, that the process of metastasis is a sequence of events that depends on tumor cell properties and interactions with the microenvironment at the sites of metastasis. In theory, inhibitors targeted at any of the steps of metastasis have the potential to inhibit metastatic progression. In vitro assays cannot simulate accurately the complex process of metastasis, and the use of appropriate animal model is necessary to model the process, and to test the impact of targeted inhibitors on the growth and development of breast cancer metastasis. Animal models for growth and metastasis of rodent and human breast cancer cells have been developed, including models that target the metastatic growth in key organs such as the bone and brain.