Recent advances in the understanding of fish myogenic regulatory factors (MRF) are described in this review. Specifically, two of the MRFs are discussed, Myf5 and Mrf4, which are encoded by a highly linked gene loci ( mrf4 and myf5) that is conserved among vertebrates. Experiments related to the expression patterns, biological functions and regulatory network of mrf4 and myf5 are highlighted, and examples of gene organizations and protein features among known vertebrate species are outlined. Furthermore, the complicated regulatory mechanisms of myf5 are discussed using zebrafish Danio rerio as a model. Multiple regulatory elements that control the specific expression of zebrafish myf5 are elucidated, including enhancer, silencer, proximal and distal elements, the interaction between proximal regulatory cassette −82/−62 and its cognate binding transcription factors, and a plausible post-transcriptional regulatory mechanism. This review article highlights a fundamental molecular mechanism of mrf4 and myf5 during fish muscle development.