As one of the major branches in biomechanics, cellular and molecular biomechanics have made much progress in mechano-biological and mechano-chemical coupling in the past decades. Cells sense various in vivo mechanical stimuli, which initiate downstream signaling via mechanosensitive proteins to balance external forces. It is required to understand what mechanical features of distinct cells are and how external forces are transduced to biochemical signals. Multi-scale integration from cellular, subcellular, to molecular level in a cell promotes the understanding of mechanosensation, mechanotransmission, mechanotransduction, and mechanoepigenetics. In this review, the progress update in cellular and molecular biomechanics is provided and relevant scientific issues, methodological approaches, and potential applications are discussed.