Toll-like receptors belong to the pattern recognition receptors family present on a variety of immune cells including normal and malignant B-cells. They act as immediate molecular sentinels of innate immunity but also act as a molecular bridge between the innate and the adaptive immune response; distinct Toll-like receptors are able to bind specific pattern molecules of bacteria, viruses and autoantigens. In this review we will briefly introduce the Toll-like receptor family and their expression pattern, signaling and function in the B cell context; following we will summarize the published data on TLR in chronic lymphocytic leukemia, and we will discuss their emerging role in the modulation of leukemia pathobiology.