Homeotic genes are differentially expressed along the anteroposterior axis of animal bodies and specify the developmental fate of segments by regulating specific sets of target genes. Our studies of expression and function of Daphnia Hox genes are shedding light on how alterations in their amino acid sequence can modify arthropodan limb patterns. More precisely, the diversification of hox proteins outside of their homeodomains can dramatically affect the number and shape of Daphnia limbs, suggesting that these genic regions are key players in generating evolutionary novelties.