Changes in all aspects of HTS from compound management through to evaluation of hits and leads, strengthened by infrastructure improvements, in both automation and informatics, have made possible increased analysis and implementation of process and quality control throughout HTS. This paper focuses on the process of HTS with an emphasis on quality control, reducing the variability of all the processes that have an impact on the final result, and argue that by increasing the quality of the entire process that data mining of primary screening data is in fact possible and will reduce cycle times to medicinal chemistry.