The discovery that small double stranded RNAs mediate RNA interference in mammalian cells opened the way to the therapeutic use of siRNA. siRNA has the properties well suitable for medicine, which of high selectivity, high efficacy with low dose and natural components of cells. While siRNAs are expected to be epoch-making new drugs, such as a biotech-based medicine, there are several problems concerning side effects and bioavailability to be solved, such as interferon response, off-target activity and short half-life in blood circulation. Here, I will discuss with problems that face therapeutic application of RNA interference.