Since the advent of strategies capable of manipulating the germline of mice, there has been a rapid expansion in the number of murine models of intestinal cancer. These have largely been developed with the specific aim of elucidating the molecular mechanisms underlying tumour initiation and progression. In attempting this goal, these models have become increasingly sophisticated, allowing ever more precise recapitulation of the genetic events that underlie human disease. Such technological advances include both temporal and spatial control over mutant allele expression. This review highlights some of notable recent advances using these approaches, with particular focus upon the role of a number of key signalling pathways, DNA repair mechanisms and inflammation.