Chronic lymphocytic leukemia (CLL) is the most common form of leukemia among adults in the Western world, with an incidence of approximately 1 out of 100,000 patients per year. CLL is characterized by the clonal expansion of immature CD5(+) B cells. Although cytotoxic agents remain the mainstay of therapy, the disease of up to 20% of patients is not controlled with standard therapies. Therefore, there remains a need for novel therapeutic strategies. MicroRNAs (miRNAs or miRs), first identified nearly two decades ago, are noncoding RNAs that have the capacity for simultaneous regulation of tens to hundreds of genes. An association between CLL-associated chromosomal abnormalities and miRNA deregulation is beginning to emerge. miRNAs may play a biological role in the pathogenesis of CLL: specific miRNAs (miR-15a and miR-16-1) are located at a chromosomal region (13q14.3) that is often absent in patients with CLL. These same miRNAs are relevant to cellular phenotype and in vivo development of disease. This finding has led to a rapidly expanding series of investigations linking miRNAs to CLL. As a result, miRNAs are currently under investigation as diagnostic and prognostic biomarkers as well as potential therapeutic targets in CLL.