Campuzano, SusanaPedrero, MaríaBarderas Manchado, RodrigoPingarrón, José M2023-04-272023-04-272022-04Adv. Mater. Technol. 2022,7:2200310.2365-709Xhttp://hdl.handle.net/20.500.12105/15916Electrochemical biosensors continue to evolve at an astonishing pace, con-solidating as competitive tools for determining a wide range of targets and relentlessly strengthening their attributes in terms of sensitivity, selectivity, simplicity, response time, and antifouling ability, making them suitable for getting a foothold in real-world applications. The design and exploitation of nanostructured or multifunctional nucleic acid or peptide biomaterials are playing a determinant role in these achievements. With the aim of high-lighting the potential and opportunities of these biomaterials, this perspec-tive article critically discusses and overviews the electrochemical biosensors reported since 2019 involving nanostructured and multifunctional DNA biomaterials, multifunctional aptamers, modern peptides, and CRISPR/Cas systems. The use of these biomaterials as recognition elements, electrode modifiers (acting as linkers or creating scaffolds with antifouling properties), enzyme substrates, and labeling/carrier agents for signal amplification is discussed through rationally and strategically selected examples, concluding with a personal perspective about the challenges to be faced and future lines of action.engVoRhttp://creativecommons.org/licenses/by-nc/4.0/AntifoulingEmpowered electrochemical biosensorsNanostructured and/or multifunctional biomaterialsNucleic acidsPeptidesAtribución-NoComercial 4.0 Internacional7220031010.1002/admt.2022003102365-709XAdvanced Materials Technologiesopen access