MicroRNAs (miRNAs) are small (∼18-25 nucleotides), endogenous, noncoding RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or the inhibition of protein translation. miRNAs are predicted to target up to one-third of all human mRNAs. Each miRNA can target hundreds of transcripts and proteins directly or indirectly, and more than one miRNA can converge on a single target transcript; thus, the potential regulatory circuitry afforded by miRNAs is enormous. Increasing evidence is revealing that the expression of miRNAs is deregulated in cancer. High-throughput miRNA quantification technologies provide powerful tools to study global miRNA profiles. It has become progressively more apparent that, although the number of miRNAs (∼1,000) is much smaller than the number of protein-coding genes (∼22,000), miRNA expression signatures more accurately reflect the developmental lineage and tissue origin of human cancers. Large-scale studies in human cancer have further demonstrated that miRNA expression signatures are associated not only with specific tumor subtypes but also with clinical outcomes.