Biofilms are complex three-dimensional structures formed at interfaces by the vast majority of bacteria and fungi. These robust communities have an important detrimental impact on a wide range of industries and other facets of our daily lives, yet their removal is challenging owing to the high tolerance of biofilms towards conventional antimicrobial agents. This key issue has driven an urgent search for new innovative antibiofilm materials. Amongst these emerging approaches are highly promising materials that employ aqueous-soluble macromolecules, including peptides, proteins, synthetic polymers, and nanomaterials thereof, which exhibit a range of functionalities that can inhibit biofilm formation or detach and destroy organisms residing within established biofilms. In this Review, we outline the progress made in inhibiting and removing biofilms using macromolecular approaches, including a spotlight on cutting-edge materials that respond to environmental stimuli for "on-demand"antibiofilm activity, as well as synergistic multi-action antibiofilm materials. We also highlight materials that imitate and harness naturally derived species to achieve new and improved biomimetic and biohybrid antibiofilm materials. Finally, we share some speculative insights into possible future directions for this exciting and highly significant field of research.