Skin is the body's largest organ and is responsible for the transduction of a vast amount of information. This conformable material simultaneously collects signals from external stimuli that translate into information such as pressure, pain, and temperature. The development of an electronic material, inspired by the complexity of this organ is a tremendous, unrealized engineering challenge. However, the advent of carbon-based electronics may offer a potential solution to this long-standing problem. In this Account, we describe the use of an organic field-effect transistor (OFET) architecture to transduce mechanical and chemical stimuli into electrical signals. In developing this mimic of human skin, we thought of the sensory elements of the OFET as analogous to the various layers and constituents of skin. In this fashion, each layer of the OFET can be optimized to carry out a specific recognition function. The separation of multimodal sensing among the components of the OFET may be considered a "divide and conquer" approach, where the electronic skin (e-skin) can take advantage of the optimized chemistry and materials properties of each layer. This design of a novel microstructured gate dielectric has led to unprecedented sensitivity for tactile pressure events. Typically, pressure-sensitive components within electronic configurations have suffered from a lack of sensitivity or long mechanical relaxation times often associated with elastomeric materials. Within our method, these components are directly compatible with OFETs and have achieved the highest reported sensitivity to date. Moreover, the tactile sensors operate on a time scale comparable with human skin, making them ideal candidates for integration as synthetic skin devices. The methodology is compatible with large-scale fabrication and employs simple, commercially available elastomers. The design of materials within the semiconductor layer has led to the incorporation of selectivity and sensitivity within gas-sensing devices and has enabled stable sensor operation within aqueous media. Furthermore, careful tuning of the chemical composition of the dielectric layer has provided a means to operate the sensor in real time within an aqueous environment and without the need for encapsulation layers. The integration of such devices as electronic mimics of skin will require the incorporation of biocompatible or biodegradable components. Toward this goal, OFETs may be fabricated with >99% biodegradable components by weight, and the devices are robust and stable, even in aqueous environments. Collectively, progress to date suggests that OFETs may be integrated within a single substrate to function as an electronic mimic of human skin, which could enable a large range of sensing-related applications from novel prosthetics to robotic surgery.