Down syndrome (DS) is the most common chromosomal anomaly among live born infants, occurring at a frequency of one in 700 live births. Individuals with DS are at increased risk for several endocrinological conditions, including hypothyroidism, growth retardation, diabetes mellitus, and obesity. The reason for the increased risk of obesity in DS individuals is unclear, but several mechanisms have been suggested, including a decreased resting metabolic rate and differences in physical activity patterns. Obesity and related morbidity and mortality are emerging as important long term consequences, with the increase in the life expectancy of people with DS. Adipokines such as leptin, which is a hormone secreted by adipocytes, acting in the hypothalamus to suppress appetite and regulate body weight, have been implicated in the pathophysiology of obesity. Leptin is a hormone secreted by adipocytes, acting in the hypothalamus to suppress appetite and regulate body weight. In this book we tried to highlight the hormonal key players for the development of obesity in children with Down syndrome.