Ion channels are important therapeutic targets which are modulated by a range of currently prescribed drugs. Most of these were developed empirically by traditional pharmacology without knowing their precise target, and the discovery of novel ion channel drugs by high-throughput molecular approaches has proven challenging. A key stumbling-block has been the development of biologically relevant assays with the capacity for randomly screening sizeable compound libraries. While various screening formats exist, e.g., using ion- or voltage-sensitive fluorescent dyes, these lack the precision, temporal resolution, and voltage control normally required for monitoring channel modulation. On the other hand, traditional electrophysiology is too slow, technically demanding, and labor intensive for primary screening. Recently, these limitations have been addressed by the development of automated electrophysiology instruments. While retaining much of the fidelity and precision of electrophysiology, these systems also address the main disadvantages by using automation to increase throughput and "de-skill" the process. Though the capacities currently attainable are not yet compatible with primary screening, these instruments are nevertheless having a significant impact on drug discovery. By providing high quality, information-rich assays for medium-throughput secondary screening, these instruments bridge significant gaps that, historically, have hampered the early ion channel drug discovery pipeline.