Despite intense investigation, major gaps remain in our understanding of the cellular mechanisms that underlie the actions of insulin, as well as the regulation of the enzymes and transport proteins crucial to the orderly control of glucose metabolism. In recent years, the compartmentalization of signaling molecules and metabolic enzymes has been suggested to play an important role in ensuring metabolic balance. We will discuss examples of recent findings, suggesting that spatial compartmentalization and protein translocation might be the keys to understanding the specificity of insulin in the regulation of glucose metabolism.