Advances in human genome sequencing technologies now enable genome-wide association studies (GWAS) across large populations, providing insights into the genetic origins of disease. The combination of GWAS with functional genomic analyses (e.g. CRISPR-Cas9 screens), allows identification of pathways and targets with therapeutic potential. Prior to the initiation of drug discovery efforts, validation of these targets is required, often involving the use of chemogenomic tool molecules to build confidence that a ligand can cause a diseasemodifying effect. For a large proportion of the proteome no tool molecules have been reported, therefore, platforms for rapid ligand discovery are required to enable translation of genomic analyses into medicines. The scientific community has typically relied upon highthroughput screening (HTS) for the identification of tool molecules, which is often slow and resource intensive. Bindingdriven assays, such as Affinity Selection Mass Spectrometry (ASMS) and DNA Encoded Libraries (DELs) have recently been developed to accelerate ligand discovery through the efficient screening of large libraries (10 6 -10 12 compounds). While these approaches are powerful, they employ lead-like libraries (MW>300) that generate hits that may suffer from sub-optimal ligand efficiency and can prove challenging to optimise. Additionally, the upfront investment in library generation, and sample handling, limits the accessibility of this screening strategy to the broader scientific community. Fragment-based lead discovery (FBLD) offers a complementary approach. The use of low molecular weight fragments enables effective coverage of chemical space with a smaller number of molecules, to identify weak but highly efficient interactions. Fragment hits can subsequently be optimised into more potent binders with drug-like properties, as has been demonstrated by the discovery of numerous clinical candidates by FBLD (e.g. FDA approved therapeutics: vemurafenib, venetoclax, and erdafitinib ). The primary challenge associated with fragment screening is the requirement for highly sensitive screening technologies to detect weak fragment-protein interactions. Historically, fragment screening has relied upon NMR monitoring techniques and surface plasmon resonance (SPR), but these approaches are often resource intensive. Furthermore, methods for hit validation and binding site identification (e.g. structural studies) are then required to enable the appropriate triaging and optimisation of fragment hits. Evolution of next generation fragment screening technologies would facilitate more rapid discovery of protein ligands.