Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world and exists as subtypes with very different clinical courses. CLL is generally described as a disease of failed apoptosis. Apoptosis resistance may stem from a combination of microenvironmental survival signals as well as from intrinsic alterations in the apoptotic machinery within the CLL cell. The molecular mechanism involved in controlling apoptosis in CLL is complex and is influenced by many factors, including Bcl-2 family proteins, which are critical regulators of cell death. Here we review the significance of apoptosis dysregulation in CLL, focusing on the role of Bcl-2 and related Bcl-2 family proteins, such as Bax and Mcl-1. The differential properties of the newly described subsets of CLL are also highlighted.