From telescope lenses to optical fibers and smartphone screens, glasses have been key enablers in human history. Unlike crystalline materials, glasses can virtually feature any composition and stoichiometry, which creates limitless opportunities to develop new glass formulations with unusual properties. However, this large compositional space renders traditional Edisonian trial-and-error discovery approaches poorly efficient. Accelerating the discovery of new glasses requires the genome of glass to be decoded, that is, to identify and decipher how the basic structural building blocks of glasses control their engineering properties—in the same way as the human genome offers information that serves as a blueprint for an individual’s growth and development. Here, we review some of our recent effort in that direction. Our approach combines molecular dynamics simulations with topological constraint theory—a simple, yet powerful framework that can be used to predict the compositional dependence of glass properties or pinpoint promising compositions with tailored functionalities. In this review, we report how we used this approach to understand the origin of glass-forming ability as a balance between atomic flexibility and internal stress, predict the mechanical properties of glasses, and tune the chemical reactivity of silicate glasses.