MicroRNA (miRNA) control has emerged as a critical regulatory principle in the mammalian immune system. Genetic ablation of the miRNA machinery, as well as loss or deregulation of certain individual miRNAs, severely compromises immune development and response and can lead to immune disorders like autoimmunity and cancer. Although individual miRNAs modulate protein output from hundreds of target genes, they may impact physiological processes by regulating the concentrations of just a few key cellular proteins that may be components of a single or of functionally interrelated pathways in a given cellular context.