In the current era of effective anti-retroviral therapy, immuno-compromised patients with HIV-1 infection do live long enough to suffer diseases caused by many opportunistic infections, such as herpes simplex virus type 1 and type 2 (HSV-1/2). An estimated two-thirds of the 40 million individuals that have contracted HIV-1 worldwide are co-infected with HSV-1/2 viruses, the causative agents of ocular, oro-facial and genital herpes. The highest prevalence of HIV-1 and HSV-1/2 infections is confined to the same regions of Sub-Saharan Africa. HSV-1/2 infections affect HIV-1 immunity, and vice versa. While important research gains have been made in understanding herpes and HIV immunity, the cellular and molecular mechanisms underlying the crosstalk between HSV-1/2 and HIV-1 co-infection remain to be fully elucidated. Understanding the mechanisms behind the apparent HSV-1/2/HIV-1 negative immuno-synergy may be the key to successful HSV-1/2 and HIV-1 vaccines; both vaccines are currently unavailable. An effective herpes immunotherapeutic vaccine would in turn - indirectly - contribute in reducing the HIV epidemic. The purpose of this review is: (i) to summarize the current trends in understanding  the negative immuno-crosstalk between HIV-1 and HSV-1/2 infections; and (ii) to discuss the possibility of developing a novel mucosal herpes immuno-therapeutic strategy or even a combined or chimeric immunotherapeutic vaccine that simultaneously targets HIV-1 and HSV-1/2 infections. These new trends in immunology of HSV-1/2 and HIV-1 co-infections should become part of current efforts in preventing sexually transmitted infections. The alternative is needed to balance the ethical and financial concerns associated with the rising number of unsuccessful mono-valent clinical vaccine trials.