The maintenance and expansion of the malignant B-cell chronic lymphocytic leukemia (B-CLL) clone is primarily related to the genetic events induced by various inherited or environmental processes that lead to transformation. However, the overall process of leukemic B-cell clone survivorship is also linked to a complex circuitry of cytokines and chemokines that act in both autocrine and paracrine pathways. Importantly, stromal cells, dendritic cells, endothelial cells, nurse cells, and various immune cells contribute to this cytokine/chemokine array, which ultimately contributes to the behavior of the CLL B cell. Apparent physical association of the leukemic CLL B cell with these various cell types suggests that there is significant cellular crosstalk that assists in the induction of a microenvironment favorable to the leukemic CLL B cell.