It is now generally accepted that hybrid skeletal muscle fibres are not experimental artefacts, but complex molecular systems that expand the functional repertoire of the muscle to which they belong. The purpose of this review is to highlight the cognitive value of hybrid fibres by discussing several insights into skeletal muscle biology produced by studies using hybrid fibres and/or muscles containing hybrid fibres. There is strong evidence that hybrid fibres can be used as indicators of muscle remodeling and specialization. Also, there is increasing evidence that hybrid fibres are suitable for investigating issues related to (i) the coexpression of different myosin heavy chain (MHC) isoforms and their assembly in the sarcomeric structure, (ii) the operation of the muscle cell as a multinuclear system, (iii) the tightness of the relationship between MHC isoform expression and expression of other polymorphic muscle proteins, (iv) the tightness of the relationship between MHC isoform expression and various contractile parameters, and (v) the extent of the neural input into defining the molecular and functional phenotype of skeletal muscle cells. It is predicted that, when used together with imaginatively designed methods, the hybrid fibres will further our (still limited) understanding of the regulation of muscle gene expression in multinuclear cells and of the interactions of gene products within and across different intracellular signalling pathways.