We have explored all-electronic chemical detectors based on bio-nano hybrids, where the biomolecule (DNA or protein) provides chemical recognition and a carbon nanotube (NT), graphene, or monolayer molybdenum disulfide (MoS₂) transistor enables electronic readout. Building on rapid advances in nanomaterials research and biomolecular engineering, this sensor class represents a promising approach towards sensitive and selective detection of liquid- and vapor-phase anayltes. Coupling chemistries have been developed that allow for creation of nanoelectronic and/or nanophotonic interfaces to a variety of different proteins including wild types and variants engineered for use in nanotechnology. Such bio-nano hybrids enable detection of protein cancer biomarkers, antigen from various pathogens, and small molecule targets at concentrations ~ 1 pg/mL. Single stranded DNA can be coupled to nanotubes and graphene through non-covalent functionalization and then used for its chemical recognition for small molecule analytes rather than recognition of complementary DNA. Vapor sensors based on this approach are able to discriminate between highly similar compounds such as enantiomers and very similar complex vapor mixtures characteristic of humans. More recently we have shown the promise of this system for diagnosis of disease based on volatile biomarkers. The chemical responses of this sensor class vary with the based sequence of the DNA, making this a promising pathway towards a system for machine olfaction. The work was supported by the National Science Foundation, Lockheed Martin, the Air Force Research Laboratory, Intel, and DARPA.