MicroRNAs (miRNA) are a recently discovered family of short non–protein-coding RNAs that negatively regulate gene expression. Recent studies of miRNAs highlight a requirement for cell viability. Posttranscriptional silencing of target genes by miRNAs occurs either by targeting specific cleavage of homologous mRNAs, or by targeting specific inhibition of protein synthesis. We recently identified a multisubunit protein complex termed Microprocessor that is necessary and sufficient for processing miRNA precursor RNAs. Microprocessor contains Drosha, an RNase III endonuclease, and DGCR8, a gene deleted in DiGeorge syndrome. We consider recent findings that link miRNA perturbation to cancer.