The original observation that sera from patients with chronic B-cell lymphocytic leukemia (B-CLL) contain high amounts of soluble CD23 (sCD23), which reflect disease activity and tumor load has been confirmed by numerous reports and serial determinations of sCD23 are now recognized as important indicators of disease progression. The reason why the leukemic cells over express CD23 and subsequently release large quantities of sCD23 as compared to healthy persons or patients with other lymphoproliferative disorders is still not clear. However, progress has been made in understanding the mechanism leading to the upregulation of CD23 in the leukemic cells. Following is an update on clinical data and a short review on the potential functions of CD23 as well as its regulation by Notch2 in B-CLL.