Metastasis is one of the most devastating aspects of cancer. Although it is almost always a stochastic process, tissue-specific metastasis might indicate the existence of nonrandom elements that could become effective targets for therapy. Establishment and appropriate use of organ-specific metastasis models can help us better understand the underlying biological mechanism of metastasis and aid in the design of rational and effective therapeutic strategies. This review discusses existing in vitro and animal models of liver metastasis, which are unique and practical models for investigating the mechanisms underlying tissue-specific metastasis.