Genital herpes simplex virus (HSV) infection causes recurrent genital ulcers, neonatal herpes, and increases the risk of HIV acquisition. HSV-2, the most common cause of genital herpes, is highly prevalent worldwide, with an estimated 417 million people infected between the ages of 15–49. The urgent need for a prophylactic vaccine against genital HSV has been long recognized. Multiple glycoprotein subunit vaccines candidates have been tested but none have successfully prevented HSV-2 genital ulcer disease in phase III trials. Despite these findings, there is strong interest in pursuing novel vaccine platforms to induce immune responses to protect against HSV acquisition. Therapeutic vaccines to reduce genital symptoms and viral shedding in persons already infected with HSV-2 are also being tested in early phase clinical trials. The global STI vaccine roadmap provided a framework for research priorities to move the HSV vaccine field forward. This presentation will review 1) lessons from prior clinical trials of HSV vaccines, 2) new insights into immunology of HSV infection, 3) current status of HSV vaccine pipeline, with an emphasis on candidates currently in clinical trials and 4) discussion of clinical trial design issues unique to HSV.