In mammals, adipose tissues and skeletal muscles (SkMs) play a major role in the regulation of energy homeostasis. Recent studies point to a possibility of dynamic interplay between these 2 sites during development that has pathophysiological implications. Among adipose depots, brown adipose tissue (BAT) is the major energy-utilizing organ with several metabolic features that resemble SkM. Both organs are highly vascularized, innervated, and rich in mitochondria and participate in defining the whole-body metabolic rate. Interestingly, in large mammals BAT depots undergo a striking reduction and concomitant expansion of white adipose tissue (WAT) during postnatal development that shares temporal and molecular overlap with SkM maturation. The correlation between BAT to WAT transition and muscle development is not quite apparent in rodents, the predominantly used animal model. Therefore, the major aim of this article is to highlight this process in mammals with larger body size. The developmental interplay between muscle and BAT is closely intertwined with sexual dimorphism that is greatly influenced by hormones. Recent studies have pointed out that sympathetic inputs also determine the relative recruitment of either of the sites; however, the role of gender in this process has not been studied. Intriguingly, higher BAT content during early postnatal and pubertal periods positively correlates with attainment of better musculature, a key determinant of good health. Further insight into this topic will help in detailing the developmental overlap between the 2 seemingly unrelated tissues (BAT and SkM) and design strategies to target these sites to counter metabolic syndromes.