The nuclear receptor superfamily comprises a large group of transcription factors that play a key regulatory role in development and homeostasis of multicellular organisms. A special feature of nuclear receptors is their ability to bind to condensed chromatin templates, which makes them important initiators of gene transcription. Moreover, the ability of nuclear receptors to sequentially recruit a variety of transcription factors and coregulators to target promoters and to orchestrate the whole process of gene transcription confirms their biological significance and stimulates intensive research and a high level of scientific interest in this field. In this review, we summarise current knowledge regarding the structure and function of nuclear receptors as principal regulators of gene expression. Emphasis is given to the molecular mechanisms of nuclear receptor-mediated transcriptional activation and repression including recent progress made in this area.