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The 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Z. Fire and Craig C. Mello for their discovery of RNA interference (RNAi). RNAi is a biological process in which RNA molecules can silence (inhibit) or up- or down-regulate gene expression, typically by causing the destruction of specific messenger RNA (mRNA) molecules. This collection of articles begins with an introduction to RNAi, and proceeds to describe uses of this technology in various approaches to disease treatment, including gene therapy. Several laboratory protocols for silencing genes via RNAi are also provided, as are protocols for down-regulating and then rescuing those down-regulated genes, which demonstrates specificity of the approach. This e-book — a curated collection from eLS, WIREs, and Current Protocols — offers a fantastic introduction to the field of RNA interference for students or interdisciplinary collaborators.