Alterations in miRNA genes play a critical role in the pathophysiology of many, perhaps all, human cancers. Loss or amplification of miRNA genes has been reported in a variety of cancers, and altered patterns of miRNA expression may affect cell cycle and survival programs. Downregulation of suppressor miRNA is accompanied by the hyperexpression of the oncogenic PCG targets (marked in blue), while overexpression of oncogenic miRNA is followed by downregulation of suppressor PCG targets (marked in red). The two paradigms presented in this Review, miR-15a/miR-16-1 cluster and miR-21, are shown in correlation with their main identified targets.