Mesenchymal stem cells (MSCs) have a capacity to differentiate into the chondrogenic lineage and are a valuable allogenic source for cartilage tissue engineering. However, they still have critical limitations of relatively inefficient chondrogenic differentiation in vitro and of dedifferentiation and/or hypertrophic changes at late stages of differentiation. Numerous approaches using biochemical and mechanical factors have been tried but have so far failed to overcome these problems. Recent studies by other groups and ours have shown that low-intensity ultrasound (LIUS) is an efficient tool for promoting the chondrogenic differentiation of MSCs both in vitro and in vivo. A series of our experiments suggests that LIUS not only induces chondrogenic differentiation of MSCs but also has diverse additional activities that enhance the viability of MSCs, increase possibly the integrity of the differentiated tissues and delays hypertrophic changes during differentiation. Therefore, LIUS could be an innovative and versatile tool for chondrogenic differentiation of MSCs and for cartilage tissue engineering.