Nutrition plays a pivotal role in the regulation of growth hormone (GH) and insulin-like growth factor 1 (IGF 1) secretions; GH and IGF 1 in turn significantly influence the use of nutrients in humans and animals. Fasting, and caloric or protein restriction increase circulating values of GH and decrease those of IGF 1. These findings strongly suggest peripheral growth hormone resistance. Mechanisms accounting for this GH refractoriness could be a marked reduction in GH receptors, a decrease in binding of GH to its receptor, or post-receptor phenomena. Peripheral refractoriness to IGF 1 has also been described during caloric intake restriction. Metabolic effects of GH and IGF 1 are strongly dependent on a protein anabolic mechanism, and modifications of circulating levels of these hormones could be explained as an adaptation to the nutritional microenvironment of the cells. Because of the potent anabolic effects of GH and IGF 1 on protein metabolism, several authors have proposed treating severe catabolic states with GH or IGF 1. In humans both hormones seem to enhance protein anabolism but only for short periods. Secondary effects are mainly hypoglycemia with IGF 1 and hyperglycemia with GH. The combination of GH + IGF 1 could be a suitable approach to obtain a synergistic effect on protein metabolism and achieve normal blood glucose concentrations.