Size is a fundamental feature of biology that affects physiology at all levels, from the organism to organs and tissues to cells and subcellular structures. How size is determined at these different levels, and how biological structures scale to fit together and function properly are important open questions. Historically, amphibian systems have been extremely valuable to describe scaling phenomena, as they occupy some of the extremes in biological size and are amenable to manipulations that alter genome and cell size. More recently, the application of biochemical, biophysical, and embryological techniques to amphibians has provided insight into the molecular mechanisms underlying scaling of subcellular structures to cell size, as well as how perturbation of normal size scaling impacts other aspects of cell and organism physiology. This thesis is comprised of three projects which examine mechanisms of size scaling in Pipid frogs at the subcellular, cellular, and organismal levels. We find that molecular mechanisms for spindle size scaling in eggs of the small frog Hymenochirus boettgeri are not conserved with those of Xenopus species. Instead, a novel mechanism operates involving post-translational modification of microtubule depolymerizing motor protein kif2a to modulate spindle size. We also characterize size scaling in viable Xenopus laevis/ Xenopus tropicalis hybrids and use this system to establish a novel screening method for candidate genes involved in size control. Finally, we characterize size scaling in the rare dodecaploid Xenopus longipes to examine how genome size impacts cell size and other traits such as developmental rate. The well-documented correlation between genome size and cell size is conserved in somatic cells but not in early development, which proceeds more slowly in Xenopus longipes than in Xenopus laevis, thus highlighting an important correlation between genome size and developmental rate.