Structural superlubricity (SSL) at layered material interfaces is an exciting and vibrant field of research, offering vast opportunities to achieve ultra-low friction and wear with numerous potential technological applications. At increasing length-scales, new physical and chemical energy dissipation pathways emerge that threaten to push the system out of the superlubric regime. Physical inhibitors of SSL are primarily associated with in-plane elasticity, out-of-plane corrugation, moiré superlattices, grain boundaries, and lattice defects. Chemical mechanisms that may suppress superlubric behavior include interlayer bonding, wear, and external contaminants. In this article, we review these and other challenges facing the scaling-up of structural superlubricity, as reflected in recent experimental and theoretical studies. We further offer perspectives on future directions for realizing and manipulating macroscale superlubricity and outline several technological opportunities that large-scale SSL entails.