Polymeric pharmaceuticals are drugs whose active components are polymers, neither a drug carrier nor a prodrug. The underlying concept for this class of therapeutic agents is to use high molecular weight and functional characteristics of polymers to selectively recognize, sequester, and remove low molecular weight and macromolecular disease-causing species in the intestinal fluid. The high molecular weight nature of these polymeric drugs makes them systemically nonabsorbed, thus providing a number of advantages including long-term safety profiles over traditional small molecule drug products. This Article summarizes some of the most recent efforts for the discovery and development of sequestrant-based polymeric drugs. Examples include sequestration of low molecular weight species such as bile acids, phosphate, and iron ions as well as polyvalent interactions to bind toxins, viruses, and bacteria using functional polymers. Furthermore, use of polymeric surfactant for treating sickle cell anemia has been reviewed.