Readily available chemicals keep increasing rapidly in number while the need for novel chemical matter for drug targets remains at an all time high. Recently, tera-scale virtual libraries have become available enabling trillions of compounds for purchase and deployment in hit discovery projects. To support the ever-growing access to vast chemical space Schrödinger has developed a plethora of ligand-based tools facilitating efficient and locally-deployable screening campaigns for pharmacophores, ligand shape, and fingerprint methodologies at increasing library sizes, from enumerated to virtual spaces. In this presentation we will review these technologies as well as chemical space where they are most applicable.