Muscle performance is in part dictated by muscle fibre composition and a precise understanding of the genetic and acquired factors that determine the fibre type profile is important in sport science, but is also relevant to neuromuscular diseases and to metabolic diseases, such as type 2 diabetes. The dissection of the signalling pathways that determine or modulate the muscle fibre phenotype has thus potential clinical significance. In this brief review, I examine the evolution of the notion of muscle fibre types, discuss some aspects related to species differences, point at problems in the interpretation of transgenic and knockout models and show how in vivo transfection can be used to identify regulatory factors involved in fibre type diversification, focusing on the calcineurin-nuclear factor of activated T cells (NFAT) pathway.