Electrostatic Discharge (ESD) is a significant hazard to electronic components and systems. Based on a specific processing technology, a given circuit application requires a customized ESD consideration that includes the devices’ operating voltage, leakage current, breakdown constraints, and footprint. As new technology nodes mature every 3-5 years, design of effective ESD protection solutions has become more and more challenging due to the narrowed design window, elevated electric field and current density, as well as new failure mechanisms that are not well understood. The endeavor of this research is to develop novel, effective and robust ESD protection solutions for both emerging technologies and modern complementary metal–oxide–semiconductor (CMOS) technologies. The Si nanowire field-effect transistors are projected by the International Technology Roadmap for Semiconductors as promising next-generation CMOS devices due to their superior DC and RF performances, as well as ease of fabrication in existing Silicon processing. Aiming at proposing ESD protection solutions for nanowire based circuits, the dimension parameters, fabrication process, and layout dependency of such devices under Human Body Mode (HBM) ESD stresses are studied experimentally in company with failure analysis revealing the failure mechanism induced by ESD. The findings, including design methodologies, failure mechanism, and technology comparisons should provide practical knowhow of the development of ESD protection schemes for the nanowire based integrated circuits. Organic thin-film transistors (OTFTs) are the basic elements for the emerging flexible, printable, large-area, and low-cost organic electronic circuits. Although there are plentiful studies focusing on the DC stress induced reliability degradation, the operation mechanism of OTFTs iv subject to ESD is not yet available in the literature and are urgently needed before the organic technology can be pushed into consumer market. In this work, the ESD operation mechanism of OTFT depending on gate biasing condition and dimension parameters are investigated by extensive characterization and thorough evaluation. The device degradation evolution and failure mechanism under ESD are also investigated by specially designed experiments. In addition to the exploration of ESD protection solutions in emerging technologies, efforts have also been placed in the design and analysis of a major ESD protection device, diodetriggered-silicon-controlled-rectifier (DTSCR), in modern CMOS technology (90nm bulk). On the one hand, a new type DTSCR having bi-directional conduction capability, optimized design window, high HBM robustness and low parasitic capacitance are developed utilizing the combination of a bi-directional silicon-controlled-rectifier and bi-directional diode strings. On the other hand, the HBM and Charged Device Mode (CDM) ESD robustness of DTSCRs using four typical layout topologies are compared and analyzed in terms of trigger voltage, holding voltage, failure current density, turn-on time, and overshoot voltage. The advantages and drawbacks of each layout are summarized and those offering the best overall performance are suggested at the end