Nanopores are extremely sensitive single-molecule sensors. Recently, electron beams have been used to fabricate synthetic nanopores in thin solid-state membranes with subnanometer resolution. Here we report a new class of chemically modified nanopore sensors. We describe two approaches for monolayer coating of nanopores: (1) self-assembly from solution, in which nanopores approximately 10 nm diameter can be reproducibly coated, and (2) self-assembly under voltage-driven electrolyte flow, in which we are able to coat 5 nm nanopores. We present an extensive characterization of coated nanopores, their stability, reactivity, and pH response.