Therefore, we take a restricted approach and in the first part of the review we will provide an overview of the in vivo evidence of BCR, CD40, and TLR signaling in CLL proliferation, and in the second part of the review we will cover the in vitro data that support the role of BCR, CD40, and TLR signaling in the proliferation of CLL. This evidence concerns the gene CD40 and B-cell chronic lymphocytic leukemia.