To launch an effective antiviral immune response, cells must recognize the 
virus, activate a cytokine response, and initiate inflammatory processes. Herpes 
simplex virus 1 (HSV-1) and HSV-2 are nuclear-replicating viruses composed of a 
double-stranded DNA genome plus glycoproteins that are incorporated into a lipid 
bilayer envelope that surrounds an icosahedral capsid. Several novel receptors 
that mediate innate recognition of HSV and that activate the innate immune 
response have been identified in recent years. The host-virus interactions that 
lead to type I interferon (IFN), type III IFN, and cytokine production include 
cellular recognition of viral envelope and structural proteins, recognition of 
viral genomic DNA and recognition of virus-derived double-stranded RNAs. Such 
RNAs can interact with cellular pattern-recognition receptors, including 
Toll-like receptors and a number of cytoplasmic and nuclear receptors for virus 
DNA and virus-derived RNAs. In this review, I present a systematic overview of 
innate cellular recognition of HSV infection that leads to immune activation, 
and I discuss the implications of the known cell-host interactions. In addition, 
I discuss the use of innate stimulation to improve anti-HSV treatment and 
vaccine response and I discuss future research aims.