Cells continuously adapt to changing conditions through coordinated molecular and mechanical responses. This adaptation requires the transport of molecules and signaling through intracellular regions with differing material properties, such as variations in viscosity or elasticity. To determine the impact of regional variations on cell structure and physiology, an approach, termed bio-microrheology, or the study of deformation and flow of biological materials at small length scales has emerged. By tracking the thermal and driven motion of probe particles, organelles, or molecules, the local physical environment in distinct subcellular regions can be explored. On the surface or inside cells, tracking the motion of particles can reveal the rheological properties that influence cell features, such as shape and metastatic potential. Cellular microrheology promises to improve our concepts of regional and integrated properties, structures, and transport in live cells. Since bio-microrheology is an evolving methodology, many specific details, such as how to interpret complex combinations of thermally mediated and directed probe transport, remain to be fully explained. This work reviews the current state of the field and discusses the utility and challenges of this emerging approach.