Disruption of endocrine hormonal balance (i.e., increased levels of insulin, and reduced levels of growth hormone, GH) often occurs in pre-obesity and obesity. Using distinct intracellular signaling pathways to control cell and body metabolism, GH and insulin also regulate each other's secretion to maintain overall metabolic homeostasis. Therefore, a comprehensive understanding of insulin and GH balance is essential for understanding endocrine hormonal contributions to energy storage and utilization. In this review we summarize the actions of, and interactions between, insulin and GH at the cellular level, and highlight the association between the insulin/GH ratio and energy metabolism, as well as fat accumulation. Use of the [insulin]:[GH] ratio as a biomarker for predicting the development of obesity is proposed.