The liver is the largest organ and carries out the most complex biological functions in the body. It secretes bile, synthesizes proteins, metabolizes nutrients, hormones, and drugs, and detoxifies noxious endogenous and exogenous substrates. To accomplish all of these functions, the liver is located centrally in the body and endowed with well-designed architecture with a generous amount of blood supply. Secretion of bile is one of many important liver functions, and bile promotes digestion and absorption of essential nutrients; it also serves as a vehicle to get rid of biological waste products from the body. The biliary tree is designed not only for continuous bile secretion and flow, but also for periodic bile storage and discharge (gallbladder) at the time when food enters the small intestine. The spleen carries out many functions whose importance has been recognized only recently. This chapter will discuss the various functions of these two organs.