The development and adoption of fragment-based lead discovery is partly driven by the deployment and refinement of the technologies that enable this drug-discovery approach. Advances in the capabilities of the core discovery functions have historically impacted various elements of the discovery process. For example, early fragment screens produced more structure information earlier in a screening cascade through use of high-resolution protein-detected NMR or crystallography based screening approaches. These screens were rich in information but slow, expensive, and limited to small libraries. The wider spread adoption of ligand-detected NMR and surface plasmon resonance (SPR) binding assays, with their higher throughput and lower sample consumption, allowed fragment screening cascades to be reformulated to more closely resemble HTS. The lower cost, high-throughput, lower information single-dose experiments are performed early, followed by more information-rich, but slower and more costly structural experiments on the reduced set of characterized binders. Refinements and innovations in hardware, software, and practical methodologies have continued to advance the ease and scope of the implementation of SPR-based biosensors. In this chapter we describe a number of these recent advances that streamline the workflow and can give screening groups more options and flexibility to bring higher information content data to teams earlier. With these tools in hand, third-generation screening cascades can be proposed that can give fragment discovery efforts more traction and momentum in the early lead-discovery setting.