One important discovery in plant pathology over recent decades is the natural antiviral defense mechanism mediated by RNA interference (RNAi). In antiviral RNAi, virus infection triggers Dicer processing of virus-specific double-stranded RNA into small interfering RNAs (siRNAs). Frequently, further amplified by host enzyme and cofactors, these virus-derived siRNAs direct specific virus clearance in an Argonaute protein-containing effector complex. The siRNAs derived from viruses and viroids accumulate to very high levels during infection. Because they overlap extensively in nucleotide sequence, this allows for deep sequencing and bioinformatics assembly of total small RNAs for rapid discovery and identification of viruses and viroids. Antiviral RNAi acts as the primary defense mechanism against both RNA and DNA viruses in plants, yet viruses still successfully infect plants. They do so because all currently recognized plant viruses combat the RNAi response by encoding at least one protein as a viral suppressor of RNAi (VSR) required for infection, even though plant viruses have small genome sizes with a limited coding capacity. This review article will recapitulate the key findings that have revealed the genetic pathway for the biogenesis and antiviral activity of viral siRNAs and the specific role of VSRs in infection by antiviral RNAi suppression. Moreover, early pioneering studies on transgene silencing, RNAi, and virus−plant/virus−virus interactions paved the road to the discovery of antiviral RNAi.