Mouse models of cancer are critical tools for elucidating mechanisms of cancer development, as well as for assessment of putative cancer therapies. However, there are ongoing concerns about the value of mouse cancer models for predicting therapeutic efficacy in humans. This chapter reviews the most commonly used transplanted tumor models, including subcutaneous and orthotopic tumors in mice. It also reviews commonly utilized in vivo study endpoints. Even small improvements in predictive value achieved through careful selection of models and endpoints have the potential to have large impacts on productivity and overall drug development costs.