Chronic lymphocytic leukemia (CLL) results from the relentless accumulation of small mature, slowly dividing, monoclonal B-lymphocytes. The clinical course is heterogeneous, some patients with aggressive form of the disease progressing rapidly with early death while others exhibit a more stable, possibly, non-progressing indolent type of the disease lasting many years. Despite progress in modern treatment modalities, relapse invariably occurs and disease still remains incurable. The clinical management of CLL is therefore challenging and considerable effort has been directed towards novel therapeutic strategies aimed at reducing minimal residual disease which can increase remission duration. Recent insight into the role of dendritic cells (DCs) as pivotal antigen presenting cells that initiate immune responses may provide the basis for generating more specific and effective immune responses. Ex-vivo modified and monocyte-derived DCs represents a promising approach within the context of CLL. However, understanding the relationship between DCs and the cellular immune response is crucial in devising strategies for manipulating immune responses. After a brief survey of general properties of DCs, this review focuses on the different approaches exploiting monocyte-derived DCs in CLL, which may help to design novel strategies for phase-I clinical trials. © 2005 Taylor & Francis Group Ltd.