The RNAi for Developing Targeted Therapeutics meeting, held in Boston, included topics covering new therapeutic developments in the field of RNAi-based drug discovery. This conference report highlights selected presentations on the reversal of drug resistance using targeted siRNA or small-hairpin RNA and EnGeneIC drug delivery vehicles, the development of siRNA therapeutics for lung diseases, siRNA-based topical microbicides, locked nucleic acid-based oligonucleotides, and company-specific approaches to the development of RNAi therapeutics from Alnylam Pharmaceuticals Inc and MDRNA Inc. In addition to in vivo delivery approaches, novel RNAi-based approaches are also discussed, including dicer substrate siRNA, sd-rxRNA from RXi Pharmaceuticals Corp and a cationic liposome formulation of RNAi.