Despite of the challenges associated with the microRNA/RNA-i-based therapeutics (such as delivery limitations, instability and off-target effect) this approach has many promises and advantages over the conventional targeted-therapy. MicroRNAs/siRNAs are easy to synthesize and, can potentially target any gene including non-druggable targets. The fact that microRNA (miRNA) are evolutionarily conserved, suggests that miRNA therapeutics may have fewer side effects as compare to the artificial siRNAs. At present the miRNA/RNA-i therapeutics field is in its juvenile stage and majorities of these limitations can be overcome in the next decade or so. This forum focuses of discussions/suggestions to how to overcome the challenges associated with microRNA/RNA-i therapeutics.