The fight against chronic lymphocytic leukemia (CLL) has seen in recent years the development of new targeted therapies directed against signalling transducers and cell surface molecules. However CLL, the most common leukemia in adults in Western countries, cannot be cured and therefore represents a major burden for health care systems. The bone marrow microenvironment represents a major source of pro-survival factors for the leukemic B cells where mesenchymal stem cells and endothelial cells provide signals via direct contact or secreted factors. Thorough examination of clinical samples at the molecular level is therefore required to determine how CLL B cells communicate with their marrow environment to stimulate these cells to release pro-survival factors. This study aims at investigating the use of secreted vesicles -or exosomes- by leukemic cells to communicate with their microenvironment. A better comprehension of these mechanisms could pave the way for a targeted and personalized medicine to switch off the tumour supply in growth and survival factors for the circulating cancer cells. Newly identified molecules or signals may be further assessed as therapeutics targets and/or used as disease biomarkers and represent potential treatment and diagnosis opportunities.