Very recent developments in instrumentation and image analysis have made microscopy applicable to high-throughput screening (HTS). For 'High-Content Screening' modern automated microscopy systems provide a throughput of up to 100,000 (confocal) images, with amazingly high resolution, of cells fluorescently stained using multiple colours that are imaged simultaneously during the screen. Image analysis tools provide multi-parametric pattern extraction and quantification on-the-fly. Big pharmaceutical companies have presented image-based screens of more than 100,000 compounds, while academia has published data on large RNA interference screens for functional genomics. Numerous whole-genome sequencing projects have been completed and published. Gene annotation is still in flux. Nevertheless, about 23,000 human genes have been reliably annotated. Additionally, gene expression array technologies and proteomics have added further data on molecules present in cells and tissues. The major challenge of the present and future is to unravel the detailed function of all these gene products and their interaction. One way to gain insight, is to design oligonucleotides that induce lack-of-function phenotypes by specifically inhibiting protein production.