RNA interference (RNAi) has in the last decade seen ever increasing use in cell biology as both a tool with which most cell functions can be modulated and as a natural mechanism through which cells regulate their gene expression. As RNAi can be used to direct stem cell differentiation, enhance tissue development, modulate inflammation and control other cellular phenomenon relevant to implant medicine the potential for using RNAi to enhance regenerative medicine is huge. Unfortunately, there are a number of obstacles and special concerns that need to be addressed before the use of RNAs on scaffolds and implants can go into clinical use. A number of studies have recently started to address these problems and demonstrate both the current limitations and the great promise of the technique. In this chapter we will discuss the basic principles of RNAi, it’s applications in regenerative medicine and approaches to functionalize implants. We will describe various delivery methods for the inducer of RNAi, small interfering RNAs, in conjunction with scaffolds and how the application determines the delivery strategy. Finally, we describe how natural RNAi, mediated by microRNAs, can be manipulated by similar delivery techniques.