This textbook for graduate students provides a conceptual framework for comprehending diversity and evolutionary relationships of gene regulatory systems. It elucidates the importance and significance of the physical and chemical principles that underpin gene regulatory processes. The introductory section presents the core principles of the organization of genes, genomes, and aspects of gene regulation in three domains of life. The subsequent narrative then describes the process of gene expression as it goes from the DNA sequence embedded in the genome to the final functional protein. The book then describes how genes are regulated in different domains of life, the principal focus of the book, with considerable mechanistic details. This section also discusses the evolutionary relationships of gene regulatory systems in three domains of life: archaea, eubacteria, and eukarya. In the final section, the book underscores the potential to artificially intervene and alter gene regulation and describes attempts to re-engineer gene regulatory circuits.