The concept of vaccination came to light following Edward Jenner's classical observation on milkmaids who were protected against smallpox. However, plants lack the cellular based immunity system and thus it was not appreciated earlier that plants can also be protected from their pathogens. But phenomena like cross-protection, pathogen derived resistance (PDR), viral recovery, etc. in plants suggested that plants have also evolved immunity against their pathogens. The further advances in the field revealed that an endogenous defense system could have multiple prongs. With the advent of RNAi, it was clear that the antiviral immune responses are related to the induction of specific small RNAs. The detection of virus specific small RNAs (vsiRNA) in immunized plants confirmed their roles in the immunity against pathogens. Although many issues related to antiviral mechanisms are yet to be addressed, the existing tools of RNAi can be efficiently used to control the invading viruses in transgenic plants. It is also possible that the microRNA(s) induced in infected plants impart immunity against viral pathogens. So the small RNA molecules play a vital role in defense system and these can be engineered to enhance the immunity against specific viral pathogens.