MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that control gene expression at the post-transcriptional level. To date, over 700 human miRNA precursors with over 1,000 mature miRNAs have been reported. miRNAs are related to, but distinct from, short interfering RNAs (siRNAs). A key difference between siRNAs and miRNAs is that siRNAs require almost identical sequences to targets to exert their silencing function, whereas miRNAs usually bind to the 3-untranslated region (3-UTR) of target genes through partial sequence homology. Because of this unique feature, a single miRNA has multiple targets and thus, miRNAs could regulate a large fraction of proteincoding genes. This may explain why miRNAs play a fundamental role in regulation of diverse cellular processes such as cell growth, proliferation, differentiation and apoptosis and thus, deregulation of miRNA expression can lead to a variety of disorders including cancer. In this regard, miRNAs can function as either oncogenes or tumor suppressors. For example, miR-21 is an oncogenic miRNA which has been shown to promote tumor growth and metastasis in several types of cancers by targeting multiple tumor suppressors. Therefore, targeting miR-21 may provide a promising strategy for cancer intervention. In this review, we will discuss our current understanding of miR-21-mediated gene silencing, tumor growth and metastasis, and the potential of miR-21 as a cancer biomarker. We will also provide a perspective on targeting miR-21 for cancer therapy.