The ability to read the sequence of genes and genomes has transformed the face of biology. However, as part of the copying, storage, transfer and reading of the genetic information they harbor, genomes are subject to constant physical manipulation. In this talk, I will describe two case studies that illustrate the rich interplay between the information content of genomes and their behavior as physical objects. The first example will focus on how the genomes of viruses are packed within the tiny confines of the viral capsid and how that DNA comes out again once the virus infects a host. The second example will focus on the statistical mechanics of how cells make decisions by manipulating their genomes through protein binding.