B-cell chronic lymphocytic leukaemia (CLL) should be an ideal target for immune-mediated responses. CLL arises from B cells that can act as antigen-presenting cells (APCs), expresses unique tumour antigens, and has been shown to be a target of the allogeneic T cells which mediate a graft-versus-leukaemia effect. Despite these potential benefits, immune responses against CLL cells have been difficult to elicit. CLL induces immune defects in the host, the tumour cells are inefficient APCs, and therapies given to patients with CLL are themselves immunosuppressive. Successful vaccination approaches in this disease will require steps to overcome these difficulties, including identification of the targets of immune responses in this disease to enable monitoring of the immune response after vaccination, improved presentation of antigens, and steps to improve the immune defects that accompany this disease.