Even though chronic lymphocytic leukemia (CLL) is the most prevalent leukemia of the Western world, the development of treatment approaches for CLL has lagged behind the development of approaches to various other hematologic malignancies for a variety of reasons. In recent years, the treatment approach to patients with CLL has evolved rapidly, with the addition of several new prognostic markers, highly effective immunochemotherapy combinations, and attainment of remission up to the point of the eradication of minimal residual disease (MRD). Highly sensitive methods now available to detect MRD can detect a single CLL cell in 10(4) leukocytes using either allele-specific oligonucleotide polymerase chain reaction or four-color or six-color flow cytometry. Over the past decade, several studies have examined the possible advantage of MRD eradication in CLL. This article reviews our current understanding of MRD eradication and analyzes whether it is a desirable goal in the routine clinical treatment of CLL, which will optimize the management of individual patients.