The era of genomics has profoundly aided our understanding of the genetic changes responsible for generating diversity of metazoan form. In contrast, access to a plethora of genomes (and developmental biology in the embryos they control) has further muddled the concept of homology. Morphologically disparate animals utilize the same core genetic toolkit during development, meaning that the same genes are utilized to form vastly different structures among taxa. Did these gene activities arise due to common ancestry, or did they arrive independently? In essence, how do we determine whether a genetic program in two individuals is homologous, or convergent? This thesis attempts to answer this fundamental question using the fin to limb transition as a model paradigm. The pattern of activity of key genes (specifically Hox) that build the pectoral fins of fish and the limbs of tetrapods are extremely similar, yet the morphology of fins and limbs are very different. Did the common ancestor of fish and tetrapods contain this genetic program (homology), or were they invented separately in each group (convergence)? Here, I use comparative regulatory architecture as a foothold to elucidate this question, as homologous expression patterns are likely to utilize homologous regulatory elements. Through comparative epigenomics, sequence analysis, and functional experiments, I find that fish utilize the same overall enhancer landscapes in the development of fins as the limbs of tetrapods. Thus, the genetic program that builds fins and limbs (Hox) were present and functional in the common ancestor of fish and tetrapods, implying concrete evidence for homology between specific segments in fins and limbs. Finally, I provide functional evidence to suggest that tetrapod digits and the fin rays of fish are built using a homologous population of cells, calling into question traditional views of the evolution of the wrist and digits.