Crystallographic fragment screening (CFS) has recently matured into an important method for the early stages of drug discovery projects. It is based on high‐throughput structure determination and thus requires a high degree of automation as well as specialized workflows and robust analysis tools. Consequently, large‐scale research facilities such as synchrotrons have embraced the method, and developed platforms to perform CFS campaigns with the help of crystallography experts and specific tools. The BESSY II synchrotron, operated by the Helmholtz–Zentrum Berlin (HZB), is one of these synchrotron facilities that offer a CFS platform, named the F2X‐facility. Here, the specialized F2X workflow is described along with the relevant differences to other existing CFS platforms, and the ongoing developments aimed at supporting users of the facility. The different stages of a CFS campaign including requirements, beamline capabilities, and the software environment are detailed and explained. A unique F2X‐GO kit is featured, which allows users the possibility of performing all sample preparation in their home laboratories. Furthermore, at the HZB a computational workflow has been built to support users beyond the hit identification stage. The advantages of the F2X‐facility at HZB are described and references are provided to successfully conduct CFS.
