Structural biology is catalyzing a paradigm shift in drug discovery towards rational approaches in target identification and validation. Leveraging structural insights obtained through cryo-EM or X-ray crystallography not only enhances the efficiency of drug discovery projects in terms of time and cost, but also significantly improves the likelihood of achieving market approval. Initiating a successful project necessitates more than just a robust package for target credentialing; it demands a comprehensive strategy for the identification and optimization of potential drugs. The critical evaluation of target druggability is markedly enhanced when supported by experimentally derived structural information. This nuanced approach ensures a more thorough understanding of the technical feasibility of drug development from the project’s inception.