RNA interference (RNAi)-based pesticides are an emerging technology that represents a new mode of action for controlling pests. Prior to widespread use in agricultural settings, companies pursuing commercial sale of double-stranded (dsRNA) pesticides must seek regulatory approval. Herein, generalized examples of the regulatory framework for pesticide authorization with the United States-Environmental Protection Agency’s (US-EPA) Office of Pesticide Programs will be summarized. This book chapter will highlight characteristics unique to risk assessment for both plant-incorporated protectants (PIPs, e.g., DvSnf7 corn) and exogenously applied dsRNA products. While dsRNA pesticides are generally considered to be low-risk, robust risk assessments are still needed to support their registration. Uncertainties associated with this class of chemistry such as the potential for increased non-target exposure from the stabilization of formulated end-use products, can introduce complexities into risk assessments. Companies seeking to commercialize dsRNA products are encouraged to meet with regulators early in the research and development cycle to consult on development of pesticide registration applications to facilitate the regulatory decision-making process.