Herpes simplex virus type 2 (HSV-2) infects 530 million people, is the predominant cause of genital ulcer disease, and a key driver of HIV epidemic in subSaharan Africa. In human populations with susceptibility to HSV appears universal. In animal models, several candidate preventative and therapeutic vaccines have been successful only to fail in clinical trials, including recent null results from the prophylactic glycoprotein D2 subunit vaccine trial. However, detailed analyses of the immune suggest assays that antibody response may correlate with protective immune response, providing the first evidence of immune correlate of protection from infection. In addition, recent characterization of CD8 tissue memory cells in genital mucosa suggests that we may also identify immune correlate of HSV-2 control in the infected host. In this Symposium, I will discuss HSV-2 vaccine efforts in the context of our understanding of pathogenesis and epidemiology, as well as the current pipeline of candidate vaccines.