MicroRNAs are short non-coding RNAs that posttranscriptionally modulate the expression of multiple target genes and are thus implicated in a wide array of cellular and developmental processes. miR-155 is processed from BIC, a non-coding transcript highly expressed in both activated B and T cells and in monocytes/macrophages. miR-155 levels change dynamically during both hematopoietic lineage differentiation and the course of the immune response. Different mouse models developed recently indicate that miR-155 plays a critical role during hematopoiesis and regulates lymphocyte homeostasis and tolerance. A moderate increase of miR-155 levels is observed in many types of malignancies of B cell or myeloid origin, and transgenic over-expression of miR-155 in mice results in cancer. While the high levels of miR-155 reached transiently during the course of the immune response remain unharmful for the organism, the reason why a moderate up-regulation of miR-155 can lead to cancer remains obscure. As prolonged exposure to inflammation can lead to cancer, the permanent up-regulation of miR-155 might be a link between the two. Therefore, designing miR-155 based therapies will require a better understanding of the molecular basis of its action as well as of how miR-155 levels are regulated in a cell-specific manner.