More and more frequently, computational biomechanics deals with problems where the portion of physical reality to be modeled spans over such a large range of spatial and temporal dimensions, that it is impossible to represent it as a single space–time continuum. We are forced to consider multiple space–time continua, each representing the phenomenon of interest at a characteristic space–time scale. Multiscale models describe a complex process across multiple scales, and account for how quantities transform as we move from one scale to another. This review offers a set of definitions for this emerging field, and provides a brief summary of the most recent developments on multiscale modeling in biomechanics. Of all possible perspectives, we chose that of the modeling intent, which vastly affect the nature and the structure of each research activity. To the purpose we organized all papers reviewed in three categories: ‘causal confirmation,’ where multiscale models are used as materializations of the causation theories; ‘predictive accuracy,’ where multiscale modeling is aimed to improve the predictive accuracy; and ‘determination of effect,’ where multiscale modeling is used to model how a change at one scale manifests in an effect at another radically different space–time scale. Consistent with how the volume of computational biomechanics research is distributed across application targets, we extensively reviewed papers targeting the musculoskeletal and the cardiovascular systems, and covered only a few exemplary papers targeting other organ systems. The review shows a research subdomain still in its infancy, where causal confirmation papers remain the most common. WIREs Syst Biol Med 2017, 9:e1375. doi: 10.1002/wsbm.1375This article is categorized under: Analytical and Computational Methods > Computational Methods Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models