Due to practical and ethical concerns associated with human experiments, animal models have been essential in cancer research. Vast resources are expended during the development of new cancer therapeutics, and selection of optimal in vivo models should improve this process. Genetically engineered mouse models (GEMM) of cancer have progressively improved in technical sophistication and, accurately recapitulating the human cognate condition, have provided opportunities to accelerate the development of cancer drugs. In this article we consider the different types of animal models used for predicting the results of clinical trials of cancer drugs, and discuss the strengths and weaknesses of each in this regard. In addition, the methods of predicting in vivo models and clinical translation are discussed.