Rational design of highly focused ion channel small molecule libraries and screening strategies against ion channel drug targets will be discussed. SAR analysis obtained with our proprietary selectivity profiling and screening system resulted in effective selection of improved pre-drug candidates. ADME panel assays done in parallel with the primary assay successfully advanced the molecules into in vivo models. New IP-attractive molecules were identified for a number of targets with increased value of information based on experimental data. As current technology of ion channel library design and screening evolves, we expect the application of this approach to increase in the nearest future.