In the vertebrate central nervous system, the hindbrain is an important center for coordinating motor activity, posture, equilibrium, sleep patterns, and essential unconscious functions, such as breathing rhythms and blood circulation. During development, the vertebrate hindbrain depends upon the process of segmentation or compartmentalization to create and organize regional properties essential for orchestrating its highly conserved functional roles. The process of segmentation in the hindbrain differs from that which functions in the paraxial mesoderm to generate somites and the axial skeleton. In the prospective hindbrain, cells in the neural epithelia transiently alter their ability to interact with their neighbors, resulting in the formation of seven lineage-restricted cellular compartments. These different segments or rhombomeres each go on to adopt unique characters in response to environmental signals. The Hox family of transcription factors is coupled to this process. Overlapping or nested patterns of Hox gene expression correlate with segmental domains and provide a combinatorial code and molecular framework for specifying the unique identities of hindbrain segments. The segmental organization and patterns of Hox expression and function are highly conserved among vertebrates and, as a consequence, comparative studies between different species have greatly enhanced our ability to build a picture of the regulatory cascades that control early hindbrain development. The purpose of this chapter is to review what is known about the regulatory mechanisms which establish and maintain Hox gene expression and function in hindbrain development.