BAC transgenesis in mice has proved to be useful in exploring the regulatory mechanisms and functions of the Hox complexes. The large constructs used may include most of the relevant components of the cis-regulatory landscape. Manipulations can be accomplished without compromising the integrity of the endogenous complex which reduces the likelihood of producing confounding phenotypic abnormalities. The development of recombineering tools has been critical in providing the means necessary to make many types of precise and varied manipulations of these large constructs. Here, we will discuss the methodologies necessary to manipulate Hox complex BACs, generation of transgenic animals bearing these constructs and the utilization of these resources to address fundamental aspects of Hox biology.