We describe the nature and goals of high-throughput screening experiments, focusing on the challenges they present from the view-point of statistical analysis. We suggest graphical displays to facilitate quality control. We describe sources of systematic variation and methods to correct for it. We consider the problem of ranking compounds with respect to their effects on one cell type and we suggest a couple of procedures, depending on the available number of replicates. Finally, we explore the use of a hierarchical framework for hypothesis testing, to study the effects of compounds in multiple cell lines.