Reliable animal models are critical for evaluating immunotherapies and for defining tumor immunology paradigms. Tumor immunologists are moving away from traditional transplantation tumor systems because they do not adequately model human malignancies. Transgenic mouse models in which tumors arise spontaneously have been developed for most cancers. The models use one of three technologies: tissue-specific promoters to drive expression of SV40 large T antigen or tissue-specific oncogenes; deletion of tumor suppressor genes by gene targeting; or, conditional deletion of tumor suppressor genes or activation of oncogenes via Cre-lox technology. Knockin mice expressing human tumor antigens and gene-targeted mice with deletions for immunologically relevant molecules have been integral to advancing knowledge of the tumor-host relationship. Although animal models are becoming more sophisticated, additional improvements are needed so that more realistic models can be developed.