Background: The aim of the present study was to determine if there is a benefit for the use of Ultrasound Bone Growth Stimulators for osteoarthritis of the knee. There is evidence that osteoarthritis of the knee is primarily a disease of subchondral bone and the joint changes are secondary. Since subchondral bone in osteoarthritis contains fibrous tissue and bone growth stimulators function to change the fibrous tissue in the callus of fracture non-union into normal bone, there exists the possibility for a treatment of osteoarthritis of the knee with bone growth stimulators. Methods and Findings: Ten patients with confirmed osteoarthritis of the knee were included in this pilot study. Each patient’s pain and quality of life were assessed on three independent scales before and after treatment with non-invasive bone growth stimulators. Eight participants were treated utilizing ultrasound technology, one was treated using pulsed electromagnetic fields and one was treated with combined magnetic fields. There was a high level of significance for nine of the eleven statistical tests which were performed on three independent scales for ultrasound. The participants who were treated using pulsed electromagnetic fields and combined magnetic fields experienced greater than 80% improvement for the comprehensive scores on all three measurement scales. Conclusion: This was the first clinical use of bone growth stimulators for OA of the knee. All three technologies of ultrasound, pulsed electromagnetic fields, and combined magnetic fields were shown to be effective. The initial results are encouraging and directions for future research are discussed.