Recent investigations documented that plants can uptake and process externally applied double-stranded RNAs (dsRNAs), hairpin RNAs (hpRNAs), and small interfering RNAs (siRNAs) designed to silence important genes of plant pathogenic viruses, fungi, or insects. The exogenously applied RNAs spread locally and systemically, move into the pathogens, and induce RNA interference-mediated plant pathogen resistance. Recent findings also provided examples of plant transgene and endogene post-transcriptional down-regulation by complementary dsRNAs or siRNAs applied onto the plant surfaces. Understanding the plant perception and processing of exogenous RNAs could result in the development of novel biotechnological approaches for crop protection. This review summarizes and discusses the emerging studies reporting on exogenous RNA applications for down-regulation of essential fungal and insect genes, targeting of plant viruses, or suppression of plant transgenes and endogenes for increased resistance and changed phenotypes. We also analyze the current understanding of dsRNA uptake mechanisms and dsRNA stability in plant environments.