Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g., addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g., memory consolidation, motor learning and language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. Integral to the system are specialized HD-tDCS electrodes ( mm diameter) which allow safe and comfortable passage of current across the scalp. Here we evaluate a range of HD-tDCS electrode designs for comfort as well as test electrode over-potential, pH, and temperature. Passing 2 mA current for 22 minutes, both anodal and cathodal stimulations were evaluated independently. Subjective sensation during forearm stimulation was evaluated in 8 subjects. The benefits of skin electrical or chemical pre-conditioning were tested. Conductive Rubber, Ag, AgCl, pellet electrodes and AgCl ring electrodes were evaluated in combination with salty gels (Signa and CCNY4) and nominally electrolyte free gel (Lectron). The use of AgCl ring electrodes in combination with CCNY4 gel resulted in no significant pH, temperature, or over-potential changes under either polarity stimulation and was well tolerated by subjects. HD-tDCS may thus be applied with 2 mA per electrode for up to 22 minutes without skin irritation. Moreover, skin pre-conditioning can eliminate sensation such that HD-tDCS can be applied in a blinded fashion and under a broad range of therapeutic and performance enhancement applications. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.