Publisher Summary Hormones are secreted by glandular cells and elicit distinct responses in target cells, which contain the appropriate hormone receptors. According to their chemical nature and their mode of signal transduction, hormones are broadly classified into lipophilic and hydrophilic hormones. Lipophilic hormones, such as the classical steroid hormones, are able to cross the plasma membrane to reach their cytoplasmic or nuclear receptors. This chapter focuses on the structure and function of steroid hormone and related receptors. It outlines the identification and cloning of steroid hormone receptors and describes how the discovery of a common structural organization has led to the cloning of many other related receptors. Individual receptor functions are examined with emphasis on how receptors are activated or inhibited, how receptors bind to short DNA sequences called hormone response elements, and how the DNA–receptor complexes ultimately regulate gene transcription. It also discusses the diverse ways of signaling cross-talk that arise from interactions among the different nuclear hormone receptors and also between nuclear receptors and other transcription factors. Many known physiological functions of cloned nuclear hormone receptors are summarized and examples of human genetic diseases that are associated with nuclear hormone receptor abnormalities are provided in the chapter.