Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA 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, 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. To determine optimal stimulation electrode configurations, based on application specific constraints, we developed a HD-tDCS targeting software. High resolution (gyri/sulci precise) MRI derived finite element (FE) human head models are generated by segmenting grey matter, white matter, CSF, skull, muscle, fatty tissue, eyes, blood vessels, scalp, etc. The models comprised >10 million elements with >15 million degrees of freedom. The induced cortical electric field/current density values are calculated; activation of either radially and tangentially oriented neuronal structures are considered. Our HD-tDCS hardware (4×1-C1, 4×4-S1) currently supports the ‘4×1-Ring’ and the ‘4×4-Strip’ electrode configurations. The peak cortical electric field was matched to ‘conventional’ large rectangular-pad tDCS stimulation; however, the spatial focality was significantly enhanced by 4×1 configuration. Using patient specific head models, our software interface allows simple and rapid screening of stimulation electrode configurations. After selecting a target region, clinicians can customize the electrode configuration to balance: 1) cortical surface and brain depth stimulation focality; 2) total applied current/voltage; and 3) electrode/scalp current density. 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.