RNA interference (RNAi) is an efficient post-transcriptional gene silencing mechanism that is induced by double-stranded RNA. Applications of RNAi have gained increasing attention since the groundbreaking discovery that small interfering RNA (siRNA) molecules can be used to inhibit gene expression in mammalian cells in a sequence-specific manner. Numerous meetings have recently been held in this field, but the organiser from EF International succeeded in bringing some of the leading academic scientists and company researchers together in London to present and discuss exciting new results. Major topics covered in the meeting included the recent progress in understanding the basic mechanism of RNAi, genome-wide RNAi-based screens for target discovery, and approaches to use RNAi for target validation in cell culture and in animal models. In addition, borders and caveats of the technology, such as off-target effects and a possible induction of the interferon response by siRNA, have been discussed intensively. The use of siRNAs can be regarded as a highly potent strategy to identify and validate new targets for therapeutic interventions against cancer, viral infections, chronic pain and other diseases. Finally, siRNAs themselves hold the promise to become therapeutic agents in the near future.