:MicroRNAs (miRNAs), small non-coding RNAs that repress target genes, are a promising new focus of targeted therapeutics for cancer. miR-155 is a well-studied miRNA involved in inflammation that acts oncogenically in many hematological malignancies. Like other miRNAs, its role in these diseases is complex and nuanced, which gives particular power to its inhibition in diseased cells. This, together with increasing understanding of its key targets in cancer and the use of powerful mouse models of miR-155 in cancer, makes miR-155 an ideal target for therapeutic inhibition. Here, we review the role of miRNAs, and particularly miR-155, in cancers, and discuss progress on therapeutically targeting it, including the ongoing clinical trial of anti-miR-155 molecule Cobomarsen (MRG-106).