Modern plant breeding is still a time-consuming and costly process, even with the most advanced technologies such as gene editing. Hence, there is an urgent need to develop alternative means for plant trait manipulation and plant protection. RNA interference (RNAi) is a conserved cellular mechanism mediated by naturally occurring double-stranded RNA (dsRNA) and small RNAs (sRNAs) that can target mRNAs for destruction or transcript reduction. Here, we review the potential of technology based on RNAi, called spray-induced gene silencing (SIGS), as an alternative or adjunct to breeding for manipulation of endogenous gene expression in plants or pathogen control. SIGS based on exogenous application of RNA molecules in plants may be especially useful in reducing pest or pathogen impacts, thereby ameliorating biotic stresses and increasing the agronomic performance of crops.