Many bacterial cellular processes interact intimately with the chromosome. Such interplay is the major driving force of genome structure or organization. Interactions take place at different scales-local for gene expression, global for replication-and lead to the differentiation of the chromosome into organizational units such as operons, replichores, or macrodomains. These processes are intermingled in the cell and create complex higher-level organizational features that are adaptive because they favor the interplay between the processes. The surprising result of selection for genome organization is that gene repertoires change much more quickly than chromosomal structure. Comparative genomics and experimental genomic manipulations are untangling the different cellular and evolutionary mechanisms causing such resilience to change. Since organization results from cellular processes, a better understanding of chromosome organization will help unravel the underlying cellular processes and their diversity.