While the advent of small molecule kinase inhibitors and cell surface receptor targeted has made an extraordinary difference in the lives of patients with chronic myelogenous leukemia (CML) (1) and many lymphomas (2,3), patients with other hematologic malignancies are yet to enjoy the benefits of these types of tumor cell-specific therapies. In addition, the issue of resistance to drugs like imatinib and rituximab is becoming increasingly important (4–6). The ability to eliminate proteins, which have escaped specific targeting at the protein level or which have demonstated the ability to evolve resistant forms, is the strength of an RNA-targeted, protein-eliminating, therapeutic strategy. In addition, an ever-expanding knowledge of the biochemical and molecular pathogenesis of hematologic malignancies continues to suggest new therapeutic targets (7). Finally, “gene silencing” therapies are in principle highly specific, so if the target gene is thoughtfully chosen, damage to nontargeted tissues should be minimized, and a high therapeutic index should result (8–10).