Chronic infectious diseases are threatening human health today, and their public health severity is increasing. The efficacy issues of drugs and the increase in drug-resistant pathogens require new response strategies for chronic infectious diseases, and therapeutic vaccines have recently been proposed as an effective alternative. However, research on therapeutic vaccines is still relatively underdeveloped. To solve this problem, an accurate understanding of the status and the challenge at hand of therapeutic vaccines targeting chronic infectious diseases is needed. In the present review, we provide an overview of the latest research trends in therapeutic vaccines targeting chronic infectious diseases and summarize the development status of therapeutic vaccines currently undergoing clinical research, focusing on the cases of human papillomavirus (HPV) and Epstein-Barr virus (EBV) as representative examples. We highlight the importance of standard methods for the evaluation of therapeutic vaccine, focusing on the cell-mediated immune response, which might accelerate therapeutic vaccine development.