The recent accomplishment of a truly complete human genome has afforded a new view of chromosome structure and function that was limited 30 years ago. Here, we discuss the expansion of knowledge from the early cytological studies of the genome to the current high-resolution genomic, epigenetic and functional maps that have been achieved by recent technology and computational advances. These studies have revealed unexpected complexities of genome organization and function and uncovered new views of fundamental chromosomal elements. Comprehensive genomic maps will enable accurate diagnosis of human diseases caused by altered chromosome structure and function, facilitate development of chromosome-based therapies and shape the future of preventative medicine and healthcare.