Growth and obesity are polygenic traits largely influenced by genetics;​ however, little progress has been made towards the identification of specific genes and pathways influencing these traits. One approach to isolate quantitative trait loci (QTL) affecting growth and obesity is the use of mouse congenic strains. Congenic strains possess a genomic region from one inbred strain on the background of second strain and can be used to characterize and fine map QTL. A literature review is presented describing the status of congenic-based fine mapping strategies, with emphasis on the capture of mouse chromosome (MMU) 2 QTL (chapter 2). Next, the development and phenotypic characterization of B6.CAST^hg/hg congenic strains targeting five previously identified genomic regions harboring QTL is described (chapter 3). Each strain in this panel displayed differences in body weight and/or obesity, representing successful QTL isolation. In chapter 4, eight MMU2 congenic strains were developed by introgressing four overlapping CAST/EiJ (CAST) donor regions on two genetic backgrounds (hg/hg, HG and +/+, C57B1/6J (B6)). These strains isolated the direct effects of MMU2 QTL and confirmed interactions between QTL and the hg mutation. In addition, twenty-eight hg modifier candidate genes were sequenced in CAST and polymorphisms potentially underlying QTL were identified. The subsequent two chapters outline fine mapping of the distal region MMU2 on both an HG and B6 background. A B6.CAST^hg/hg by recipient F₂ intercross was used in chapter 5 to identify multiple QTL, some of which were sex-specific. Additionally, cis expression QTL (eQTL) for five candidate genes differentially expressed in brain tissue were mapped and represent candidate quantitative trait genes (QTG). The most intriguing cis eQTL controlled the expression of Sgnel, a gene involved in food intake, glucose homeostasis and growth hormone signaling pathways. In the final study subcongenic analysis revealed four growth and/or obesity QTL linked in repulsion in B6.CAST2D^+/+ mice, some of which also imparted maternal influences on genetically identical subcongenic mice. The results presented herein significantly advance our knowledge of the genetic architecture of growth and obesity and represent the creation of genomic resources which will guide the identification of numerous QTG.