SUMMARY The UCSF Core Center for Musculoskeletal Biology and Medicine Skeletal Biology and Biomechanics (SBB) Core supports a large and robust research base of investigators. This diverse group of basic and clinical investigators has made major contributions to the understanding of musculoskeletal health and disease. However, the ongoing research efforts by these and other investigators remain insufficient to prevent the rapidly increasing occurrence of many acquired musculoskeletal diseases in our aging population. Thus, acceleration of research that advances the prevention and treatment of skeletal diseases is urgently needed. Solutions will require a more systems-based approach with integrated research strategies and investigator communities. To meet this challenge, the SBB Core facilitates musculoskeletal research at UCSF by providing integrated, cost effective, and efficient access to rigorous musculoskeletal biology and biomechanics services. The SBB Core serves and cultivates the musculoskeletal research community across multiple campuses and disciplines by offering users seamless access to services, with Core sites at the two main UCSF campuses, easy digital conferencing, and events at multiple locations. The successful implementation of the SBB Core is anticipated to not only reduce research expenses and increase data output, rigor, and reproducibility, but also to produce robust in-depth analyses of human samples and animal models through integration of different aspects of musculoskeletal biology and biomechanics. The Core’s adoption of sophisticated and powerful large-scale ensemble as well as spatially defined, cell-specific transcriptomic and proteomic profiling will streamline quantitative analyses of musculoskeletal tissues to complement and encourage the much-needed application of big data approaches to this field. Through training and education, the SBB Core will continue to promote the entry of new investigators to the field, and it will foster a community of versatile musculoskeletal researchers with a broad set of skills and critical thinking.