The discovery of leptin in 1994 has led to remarkable advances in obesity research. We now know that leptin is a cytokinelike hormone that is produced in adipose tissue and plays a pivotal role in regulation of energy balance and in a variety of additional processes via actions in the central nervous system. This symposium review covers current understandings of neuronal leptin receptor signaling and mechanisms of obesity-related leptin resistance in the central nervous system and provides recent insights into the regulation of peripheral glucose balance by central leptin action in rodents.