A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Three myosin genes, Myh6, Myh7, and Myh7b, encode related microRNAs (miRNAs) within their introns, which control muscle myosin content, myofiber identity, and muscle performance. In the adult heart, the Myh6 gene, encoding a fast myosin, co-expresses miR-208a, which regulates the expression of two slow myosins and their intronic miRNAs, Myh7/miR-208b and Myh7b/miR-499. miR-208b and miR-499 are functionally redundant and play a dominant role in specifying muscle fiber identity by activating slow and repressing fast myofiber gene programs. These miRNAs act through a collection of transcriptional repressors of slow myofiber genes. The findings reveal that myosin genes not only encode the major contractile proteins of muscle but also influence muscle function by encoding a network of intronic miRNAs that control muscle gene expression and performance.A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Three myosin genes, Myh6, Myh7, and Myh7b, encode related microRNAs (miRNAs) within their introns, which control muscle myosin content, myofiber identity, and muscle performance. In the adult heart, the Myh6 gene, encoding a fast myosin, co-expresses miR-208a, which regulates the expression of two slow myosins and their intronic miRNAs, Myh7/miR-208b and Myh7b/miR-499. miR-208b and miR-499 are functionally redundant and play a dominant role in specifying muscle fiber identity by activating slow and repressing fast myofiber gene programs. These miRNAs act through a collection of transcriptional repressors of slow myofiber genes. The findings reveal that myosin genes not only encode the major contractile proteins of muscle but also influence muscle function by encoding a network of intronic miRNAs that control muscle gene expression and performance.