A recurring theme in the way that many pharmaceutical companies approach new technologies is that they are initially extremely enthusiastic, perhaps excessively so, but then subsequently overreact in the opposite direction, abandoning them when the first bumps in the road come along. Only a few years ago, the affection of big pharma for RNA interference (RNAi) seemed unlimited. Merck had acquired Sirna Therapeutics for $1.1 billion, and Novartis was collaborating with Alnylam, another leading developer of RNAi-based therapeutics. In 2007, Alnylam received a whopping $431 million up front from Roche and Takeda for certain rights to their RNAi technology. However, within the last year this momentum has reversed. Novartis effectively terminated its partnership with Alnylam last September by declining a $100 million option to broadly license their RNAi intellectual property. Then, in November, Roche announced its decision to exit the RNAi field, and in February of this year Pfizer announced the elimination of its Oligonucleotide Therapeutics Unit. Some observers have speculated that these moves herald the failure of RNAi as a therapeutic platform. As the former chief scientific officer of Pfizer's oligonucleotide unit and a longtime investigator in the field of oligonucleotide therapeutics, I would like to share an alternative view of the significance of these steps and of the perceptions that have led us here.