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Adipose tissue is a dynamic organ that changes mass throughout life in response to the metabolic needs of the animal. In the past three decades, significant advances have been made in delineating key extracellular and intracellular stimulators of fat cell formation or adipogenesis. In this review, the author focuses on new findings of specific inhibitors of adipogenesis. Understanding the balance between positive and negative regulators of adipogenesis has important health-related implications for anti-obesity medical therapy and lipodystrophy.Adipogenesis is a highly regulated process requiring coordinated expression and activation of two main groups of adipogenic transcription factors, CCAAT/enhancer binding proteins and peroxisome proliferators activated receptor gamma. In response to hormonal and nutrient stimuli, the increased expression and activation of these transcription factors induce the expression of adipocyte-specific genes. More recently, several groups have identified extracellular inhibitors of adipocyte formation, including cytokines, lipid molecules, genistein, and protease inhibitors. Intracellular signaling molecules, which negatively regulate adipogenesis, include Pref-1, Foxo1, Foxa2, SMAD-3, WNT-10b, GATA-2 and GATA-3.The prevalence of obesity is increasing in the United States and in other westernized societies. Understanding the mechanisms of excessive energy storage in adipose tissue is necessary to develop a comprehensive strategy to prevent and treat obesity. One potential, but unrealized, approach to obesity treatment is to target excessive adipose tissue enlargement. A number of promising extra- and intracellular inhibitors of fat cell formation have been identified, but the modulation of adipose tissue mass may have both advantageous and deleterious health effects.