The transformation of paired fins into tetrapod limbs is one of the most intensively scrutinized events in animal evolution. Early anatomical and embryological datasets identified distinctive morphological regions within the appendage and posed hypotheses about how the loss, gain, and transformation of these regions could explain the observed patterns of both extant and fossil appendage diversity. These hypotheses have been put to the test by our growing understanding of patterning mechanisms that regulate formation of the appendage axes, comparisons of gene expression data from an array of phylogenetically informative taxa, and increasingly sophisticated and elegant experiments leveraging the latest molecular approaches. Together, these data demonstrate the remarkable conservation of developmental mechanisms, even across phylogenetically and morphologically disparate taxa, as well as raising new questions about the way we view homology, evolutionary novelty, and the often non-linear connection between morphology and gene expression. In this review, we present historical hypotheses regarding paired fin evolution and limb origins, summarize key aspects of central appendage patterning mechanisms in model and non-model species, address how modern comparative developmental data interface with our understanding of appendage anatomy, and highlight new approaches that promise to provide new insight into these well-traveled questions.