Cancer remains one of the leading causes of death in the Western world. Despite bold advances in therapeutic oncology, new drug development is infamously ineffective due to the lack of predictive in vitro models. Most patients that suffer from cancer do not die from the primary tumor but due to the development of metastases. And yet current in vitro screening methods for new drugs in oncology still largely target cytotoxicity or the inhibition of cell growth, in which a potential anti-metastatic activity cannot be assessed. Herein the current in vitro models in oncology are reviewed and a new rationale for the pre-clinical development of specific, anti-metastatic therapeutic agents is introduced.