The interaction between herpes simplex virus type 1 (HSV-1) and its host starts with the attachment of the virus for entry and spreading into host cells involving viral glycoproteins and host receptors. Once entered, it remains persistent as a latent infection throughout the host's life as it cannot be cleared completely by the immune system. Viral regulatory proteins and host factors determine whether the virus will enter into the acute or latent mode of infection. Acute viral infection is usually asymptomatic and self-limiting whereas latent infection may remain in the trigeminal ganglion of oropharyngeal mucosa, where it can be activated at any time depending upon the stimulus. Host innate and adaptive immune elements play important roles in limiting HSV-1 infection by interfering with viral replication but are unable to remove the virus completely. In this review, we update how the major proteins involved in entry and pathogenesis of viruses and immune responses against infection.