Several microRNAs (miRNAs) have been implicated in tumor development based on both changes in their expression patterns and gene structural alterations in human tumors. However, we are only now beginning to see how miRNAs interact with classic oncogene and tumor suppressor mechanisms. Several recent studies have implicated the miR-34 family of miRNAs in the p53 tumor suppressor network. The expression of miR-34a, miR-34b, and miR-34c is robustly induced by DNA damage and oncogenic stress in a p53-dependent manner. When overexpressed, miR-34 leads to apoptosis or cellular senescence, whereas reduction of miR-34 function attenuates p53-mediated cell death. These findings, together with the fact that miR-34 is down-regulated in several types of human cancer, show that miRNAs can affect tumorigenesis by working within the confines of well-known tumor suppressor pathways.