Herpesviridae comprises a large family of double-stranded DNA viruses that infect both animals and humans. Eight herpseviruses are known to infect humans: herpes simplex virus type-1 and -2, varicella zoster virus, human cytomegalovirus, Epstein–Barr virus, human herpesvirus 6 type-A and -B, human herpesvirus type-7 and -8 or Kaposi's sarcoma virus. Despite the fact that the past two decades have been evolutionary in the development of antiviral agents, therapeutic choices are restricted by limited efficacy and toxicity. Viral infections remain the cause of significant mortality worldwide, thus indicating the high medical need for the introduction of novel promising compounds in the antiviral chemotherapy era. This review focuses on recent data regarding several novel groups of agents that have proved to be effective as antiherpetic drugs. The agents mentioned are those considered to be the most likely candidates for entering clinical trials and those in the process of being granted approval by the US Food and Drug Administration. The diversity in their molecular mechanism of action highlights the different perspectives currently encountered in the era of antiviral therapy.