Fat distribution is associated with metabolic risk. Differences in cellular characteristics and metabolic functions of these depots have been described, but the molecular mechanisms involved are not understood. The pathogenesis and pathophysiology of metabolic disease can be better understood by studying the molecular mechanisms that control the development and function of adipose tissue (adipogenesis). Homeobox genes are transcription factors that act during normal development and contain the homeobox, a 183bp DNA sequence coding for a 61 amino acid domain defined as homeodomain (HD). Class 1 homeobox genes (Hox genes) have a critical role in controlling positional information and tissue patterning during development. The expression of the whole HOX gene network in different deposits of normal adult human white adipose tissue (intraperitoneal, extra-peritoneal and dermis) indicate a marked expression in adipose tissue. Furthermore, this expression seems to vary in different bodily deposits of white adipose tissue and between white and brown adipose tissue. The purpose of this mini-review is to discuss the role of HOX genes in metabolic diseases.