Endogenous and exogenous forces are critical in physiology and pathology of the human body. Increasing evidence suggests that these forces, mechanics, and force-associated signaling are essential in regulating functions of living cells. Here we review advances in understanding the impact of forces and mechanics on functions and fate of embryonic stem cells, adult stem cells, and cancer stem cells and the pathways of mechanotransduction in cells. Stem-cells based models are useful in understanding how forces influence physiology, pathology, and embryonic development, which is incompletely understood, especially for mammals. We highlight increasing efforts and emerging favorable clinical outcomes in mechanomedicine, application of mechanobiology to medicine. Major progresses in mechanobiology, the pillar of mechanomedicine and mechanohealth (application of mechanobiology to health), are pivotal in understanding the life of force and making substantial advances in medicine and health.