CLL (chronic lymphocytic leukaemia) is characterized by the clonal outgrowth of B-lymphocytes with the distinctive phenotype: CD19(hi)CD5(+)CD23(+)IgM(lo). These malignant B-cells accumulate in the PB (peripheral blood) and lymphoid organs, and are generally arrested at the G(0)/G(1)-phase of cell cycle and display a resistance to apoptosis. To date, most of the CLL research has been carried out using PB samples obtained from patients with established CLL, which have proved instrumental in characterizing the disease. However, while CLL cells appear to have a defect in apoptosis in vivo, they rapidly undergo apoptosis ex vivo, suggesting that CLL cells are dependent on microenvironmental signals to enhance cell survival. One approach used to define the cellular and molecular events that govern CLL has been the development of murine models that replicate the human disease. As well as providing a deeper understanding of the potential triggers for CLL, these models provide preclinical in vivo systems to test novel therapies. The focus of the present review will be to highlight the recent advances in the development of mouse models for CLL.