A vast majority of human vaccines rely on neutralizing antibodies for protection. With the exception of vaccines against human papillomavirus, despite a great amount of dedicated effort by the scientific community, development of vaccines against sexually transmitted viruses has generally been unsuccessful. Understanding the immunobiology of the genital tract is key to designing vaccines that prevent spreading of these viruses. Recent studies demonstrate that adaptive immunity in the vaginal mucosa is uniquely regulated compared to other mucosal organs. In particular, development of virus-specific CD4⁺ and CD8⁺ T cells is critically important for antiviral defense in vagina. In this review, we provide an overview of our current understanding of a wide spectrum of immune responses in vagina – from innate viral sensing to memory development.