This Notice of Funding Opportunity (NOFO) announces the restructured Shared Instrumentation Grant (SIG) Program that consolidates three existing shared-use instrumentation programs, i.e., the Shared Instrumentation Grant program, the High-End Instrumentation Grant program, and the Basic Instrumentation Grant program. The NOFO invites applications from groups of NIH-supported investigators to purchase or upgrade a single item of state-of-the-art commercially available instrument or an integrated instrumentation system. The instruments purchased through the SIG Program require to be optimally shared among the users to ensure efficient and cost-effective research operations, enable rigorous and reproducible measurements, and encourage collaborative research and benefit broad research communities at large. The minimum award is $300,000. There is no cap on total cost of the instrument; however, the maximum award is $5,000,000. Cost sharing is required for premium instruments or special use instruments.