Conjugated polymers exhibit interesting material and optoelectronic properties that make them well‐suited to the development of biointerfaces. Their biologically relevant mechanical characteristics, ability to be chemically modified, and mixed electronic and ionic charge transport are captured within the diverse field of organic bioelectronics. Conjugated polymers are used in a wide range of device architectures, and cell and tissue scaffolds. These devices enable biosensing of many biomolecules, such as metabolites, nucleic acids, and more. Devices can be used to both stimulate and sense the behavior of cells and tissues. Similarly, tissue interfaces permit interaction with complex organs, aiding both fundamental biological understanding and providing new opportunities for stimulating regenerative behaviors and bioelectronic based therapeutics. Applications of these materials are broad, and much continues to be uncovered about their fundamental properties. This report covers the current understanding of the fundamentals of conjugated polymer biointerfaces and their interactions with biomolecules, cells, and tissues in the human body. An overview of current materials and devices is presented, along with highlighted major in vivo and in vitro applications. Finally, open research questions and opportunities are discussed.

Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low‐fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9′‐dioctylfluorene‐5‐fluoro‐2,1,3‐benzothiadiazole), in a simple one‐step substitution reaction, postpolymerization. Further, by utilizing azide‐functionalized PEG, anti‐human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site‐specifically “clicked” onto the SPN surface, which allows the functionalized SPNs to specifically target HER2‐positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics.