Hox genes provide positional information along both the body’s anterior-posterior and the limb’s proximal-distal axes. Analysis of Hox gene function in the limb has primarily focussed on their roles in skeletal patterning. Now, Deneen Wellik and co-workers (p. 4574) find that Hox11 genes are most strongly expressed in the connective tissue of the developing mouse limb, rather than the skeletal elements. Moreover, Hoxa11/Hoxd11 mutants show severe defects in tendon and muscle patterning in addition to their well-characterised role in patterning the skeleton. All defects are confined to the zeugopod region where Hox11 is known to function. These phenotypes do not appear to be a consequence of skeletal malformation, as compound mutants with a single functional Hox11 allele show no defects in the skeleton, but display significant disruption of tendons and muscles. These results define a previously unappreciated function for Hox genes in the limb, and suggest that they may act regionally to coordinate development of the various tissues of the musculoskeletal system.