Muscle fibers that power swimming in the blue crab, Callinectes sapidus, are <80µm in diameter in juveniles, but grow hypertrophically, exceeding 600µm in adults. Therefore, intracellular diffusion distances become progressively greater as the animals grow, and in adults vastly exceed those seen in most cells. This developmental trajectory makes C. sapidus an excellent model for characterizing the influence of diffusion on fiber structure. The light fibers, which power burst-swimming, undergo a prominent shift in organelle distribution with growth. Mitochondria, which require oxygen and rely on the transport of small, rapidly diffusing metabolites, are evenly distributed throughout the small fibers of juveniles, but in the large fibers of adults are located almost exclusively at the fiber periphery where oxygen concentrations are high. Nuclei, which do not require oxygen but rely on the transport of large, slow-moving macromolecules, have the inverse pattern; they are distributed peripherally in small fibers, but are evenly distributed across the large fibers, thereby reducing diffusion path lengths for large macromolecules. The dark fibers, which power endurance swimming, have evolved an intricate network of cytoplasmically-isolated, highly-perfused subdivisions that create the short diffusion distances needed to meet the high aerobic ATP turnover demands of sustained contraction. However, fiber innervation patterns are the same in both the dark and light fibers. Thus, the dark fibers appear to have disparate functional units for metabolism (fiber subdivision) and contraction (entire fiber). Reaction-diffusion mathematical models demonstrate that diffusion would greatly constrain the rate of metabolic processes without these developmental changes in fiber structure.