Three multiscale computational methodologies for biomolecular systems are described: the force-matching method for developing coarse-grained models directly from atomistic simulations; the quasi-particle approach of simulating field theory representations at the mesoscopic scale; and the multiscale-coupling method for direct information transfer between mesoscopic and atomistic scales on the fly. The statistical mechanical background for each of the methods is described in a comprehensive manner in order to highlight their theoretical foundations. Examples of various applications of these methods to model different biophysical processes are given. Combining with atomistic-level MD simulations, these three methods compose a powerful tool for bridging and spanning the multiple spatial and temporal domains that are present in many biological assemblies. Future directions of the methodology developments are also discussed.