The known classes of genes that function as tumor suppressors and oncogenes have recently been expanded to include the microRNA (miRNA) family of regulatory molecules. miRNAs negatively regulate the stability and translation of target messenger RNAs (mRNA) and have been implicated in diverse processes such as cellular differentiation, cell-cycle control and apoptosis. Examination of tumor-specific miRNA expression profiles has revealed widespread dysregulation of these molecules in diverse cancers. Although studies addressing their role in cancer pathogenesis are at an early stage, it is apparent that loss- or gain-of-function of specific miRNAs contributes to cellular transformation and tumorigenesis. The available evidence clearly demonstrates that these molecules are intertwined with cellular pathways regulated by classical oncogenes and tumor suppressors such as MYC, RAS and p53. Incorporation of miRNA regulation into current models of molecular cancer pathogenesis will be essential to achieve a complete understanding of this group of diseases.