The application of biomimetic mechanical forces for stem cell differentiation is a technique that has been on the rise in recent years. Bioreactors are being designed and constructed in order to accurately direct these forces onto stem cells in both 2D and 3D configurations. Currently, the most widely investigated mechanical forces are compressive forces and tensile strain, while a small number of researchers are making use of more complex systems of forces such as torsion, shearing and, still more complex, hemodynamic forces. The effects of these forces on mesenchymal stem cells, adipose derived stem cells, and embryonic stem cells are the most commonly explored combinations in functional tissue engineering. Fortunately, recent breakthroughs in the area of adult dental stem cells have brought viable alternatives to the use of these three cell types to the forefront of stem cell research. Yet for certain target cell types, the application of mechanical force alone is not the optimal stimulus for the induction of differentiation programs, which then requires the addition of a chemical stimulus as well. Elucidation of the optimal recipes and how these protocols affect the cells is the ultimate goal of current tissue engineering endeavors. This chapter will summarize the most current findings in functional tissue engineering, explain the importance of engineering in medical research, and describe the ways tissue engineers are attempting to understand what biochemical changes are occurring in the stem cells during the application of mechanical stress.