SUMMARY: A unique arrangement of domains makes up the common region of two otherwise very different proteins - long, elegant dystrophin, and its rather dumpy distant cousin, dystrobrevin. The two work in concert, forming the core of a large membrane-bound complex in all metazoa. Like many proteins, dystrophin and dystrobrevin have diversified in the vertebrate clade, as have their binding partners, yielding specialized complexes tailored to different cellular and subcellular locations. Disruption of several components of the complex is known to result in syndromes that include progressive myopathy, sometimes combined with cognitive defects; the best known of these is Duchenne muscular dystrophy. Despite a wealth of biochemical, cell biological and genetic information, the precise role of dystrophins, dystrobrevins and their collaborators remains unclear.