A new frontier in the development of prosthetic devices is the design of nanoscale systems which replace, augment, or support individual cells. Similar to cells, such devices will require the ability to generate mechanical movement, either for transport or actuation. Here, the development of nanoscale transport systems, which integrate biomolecular motors, is reviewed. To date, close to 100 publications have explored the design of such “molecular shuttles” based on the integration of synthetic molecules, nano- and microparticles, and micropatterned structures with kinesin and myosin motors and their associated cytoskeletal filaments, microtubules, and actin filaments. Tremendous progress has been made in addressing the key challenges of guiding, loading, and controlling the shuttles, providing a foundation for the exploration of applications in medicine and engineering.