This chapter will explain the unit automation approach to high throughput screening. The unit automation approach is predicated on the belief that automation is best implemented only to the extent that operations are standardized, i.e., if you standardize individual assay steps (or unit operations) they can be readily (and effectively) automated (1 ). If entire assay formats could be standardized, then it would make sense to automate the entire assay. However, unless assay development is severely constrained this is not possible. We have found that the majority of scientists will not agree on a standardized protocol for a particular assay format, therefore we have chosen to automate only to the level of unit operations. It should be noted that the concept of identifying, standardizing, and optimizing unit operations is applicable to fully automated screening systems as well.