Here we provide the first detailed description, based on immunohistochemistry and dissections, of the limb muscle development in the direct developing frog Eleutherodactylus coqui. We compare E. coqui with other tetrapods and discuss our results in a broad evolutionary and developmental context to address some major questions concerning the origin, evolution, and ontogeny of the tetrapod limbs. Our observations and comparisons: (1) support the “in–out” developmental mechanism of the appendicular pectoral muscles; (2) show that the protractor pectoralis and its amniote derivatives trapezius and sternocleidomastoideus clearly develop, anatomically, from the branchial muscles; (3) corroborate that the similarity between the forearm/hand and the leg/foot muscles in tetrapods is due to derived homoplasic events that occurred during the fins-limbs transition and not due to serial homology; (4) lend some support for the hypothesis that the morphological transformation of the anuran tibiale and fibulare represents a distal shift in the zeugo-autopodial border; (5) provide evidence that the identity of the tetrapod hand and foot muscles is mainly related to the topological position of the digits to which they attach; and (6) for the first time, show that apart from a proximo-distal morphogenetic gradient there is also an ulno-radial/fibulo-tibial gradient within the development of the fore- and hindlimb muscles and a dorsoventral gradient within the ontogeny of the hindlimb (but not forelimb) muscles of the frog E. coqui; the two latter gradients are seen in the ontogeny of amniotes such as chickens but are markedly different to those seen in axolotl regeneration and ontogeny. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 86–105, 2014. © 2013 Wiley Periodicals, Inc.