Skeletal muscle possesses dramatic metabolic plasticity that allows for the rapid adaptation in cellular energy transduction to meet the demands of the organism. Obesity elicits changes in skeletal muscle structure and function, resulting in the accumulation of intramuscular lipids. The accumulation of intramuscular lipids in obesity is associated with impaired skeletal muscle mitochondrial content and function. Mitochondria exist as a dynamic network that is regulated by the processes of biogenesis, fusion, fission, and mitophagy. In this review, we outline adaptations in molecular pathways that regulate mitochondrial structure and function in obesity. We highlight the emerging role of dysregulated skeletal muscle macroautophagy and mitochondrial turnover in obesity. Future research should further elucidate the role of mitophagy in observed reductions in mitochondrial content and function during obesity.