Articular cartilage possesses little capacity for endogenous repair after having been damaged by disease or trauma. Various surgical procedures depending on ingrowth of mesenchymal stem cells into the defects showed repair with fibrocartilage which is of minor quality and less resistant against physical forces. New treatment options using Tissue Engineering strategies for cartilage repair showed intriguing results. Human mesenchymal stem cells (MSC) isolated from bone marrow are becoming increasingly recognized for their potential to generate different cell types and thereby function effectively in vitro or in vivo in tissue repair. Incorporation of MSCs in suitable tissue engineering scaffolds and culture in chondrogenic medium can produce cartilage-like tissue. MSCs can be harvested from bone marrow by a small puncture of the iliac crest of patients. In contrast to chondral based repair this small procedure creates no additional harvest defect in the knee joints of the patient. Numerous publications show the beneficial influence of mechanobiological conditioning (e.g. mechanical compression, hydrostatic pressure, osmotic, shear, ultrasound) on the chondrogenic differentiation of dedifferentiated chondrocytes. In contrast to chondrocytes and cartilage explants there are few studies that examine the influence of mechanobiological stress on mesenchymal progenitor cells undergoing chondrogenesis. Using an in vitro aggregate culture system enhanced chondrogenesis of mesenchymal progenitor cells, detected by an increased extracellular matrix deposition of collagen and aggrecan, could be shown under repeated cyclic hydrostatic pressure. Similar results, with an increase in chondrogenic differentiation of mesenchymal progenitor cells could be detected, when the cells were loaded in three-dimensional matrices and subjected to cyclic, compressive load or low-intensity pulsed ultrasound. This review will summarize the current state of knowledge in the field of mechanobiological conditioning of mesenchymal stem cells and its possible clinical application.