In vitro approaches using human cancer cell lines aimed to identify and validate oncology targets, have pinpointed a number of key targets and signalling pathways which control cell growth and cell death. However, tumors are more than insular masses of proliferating cancer cells. Instead they are complex tissues composed of multiple distinct cell types that participate in homotypic and heterotypic interactions and depend upon each other for their growth. Therefore, many targets in oncology need to be validated in the context of the whole animal. This review provides an overview on how animal models can be generated and used for target identification and validation in vivo.