Many biological processes result from the effect of mechanical forces on macromolecular structures and on their interactions. In particular, the cell shape, motion, and differentiation directly depend on mechanical stimuli from the extracellular matrix or from neighboring cells. The development of experimental techniques that can measure and characterize the tiny forces acting at the cellular scale and down to the single-molecule, biomolecular level has enabled access to unprecedented details about the involved mechanisms. However, because the experimental observables often do not provide a direct atomistic picture of the corresponding phenomena, particle-based simulations performed at various scales are instrumental in complementing these experiments and in providing a molecular interpretation. Here, we will review the recent key achievements in the field, and we will highlight and discuss the many technical challenges these simulations are facing, as well as suggest future directions for improvement.