MicroRNAs (miRNAs) are short (∼22 nucleotide) RNAs that are important for the regulation of numerous biological processes. Accordingly, the expression of miRNAs is itself tightly controlled by mechanisms acting at the level of transcription as well as processing of miRNA precursors. Recently, active degradation of mature miRNAs has been identified as another mechanism that is important for miRNA homeostasis. Here we review the molecular factors and cellular conditions that promote miRNA turnover. We also discuss what is known about the physiological relevance of miRNA decay.