This review highlights the current techniques used to generate transgenic mouse models of cancer, with an emphasis on recent advances in the use of ubiquitous promoters, models that use Cre-loxP and Flip-FRT recombinase technology, inducible systems, RNAi to target genes, and transposon mutagenesis. A concluding section discusses new imaging systems that visualize tumor progression and the microenvironment in vivo. In this review, these techniques and strategies used in mouse models of cancer are highlighted, as they are pertinent and relevant to the development of zebrafish models of cancer.