In knee osteoarthritis (KOA), timely and accurate assessment of the severity is essential to help orthopedic surgeons determine the most appropriate therapeutic strategies and evaluate disease outcomes and responses for corresponding treatments. In KOA, musculoskeletal ultrasonography (MSUS) could effectively help detect various abnormalities, including synovitis, osteophytes, and cartilage damage. Further, MSUS could be used to monitor the response to different therapies in KOA, to guide local diagnostic and therapeutic procedures. In the future, applications based on continuously evolving US tools could enhance the clinical utility of MSUS in KOA.