Multichannel volume dispensing devices, such as automated liquid handlers, are widely used in drug discovery assays and other high-throughput screening processes. The performance of these systems is heavily based on the ability to deliver proper volumes of specific reagents. Discussed herein is the recent research on broadening existing methods for accurately assessing liquid-handler performance when dispensing complex or nonaqueous reagents. Accurate and reliable adjustment of liquid-handler protocols for varied reagent types could have far-reaching adoption in all scientific communities.