According to estimates from the UNAIDS Global Report 2010 around 33.3 million adults were living with HIV/AIDS at the end of 2009, the majority of them in developing countries. More than 50% adults living with HIV/AIDS are women. In the world, more than 90 percent of all adolescent and adult HIV infections have resulted from heterosexual intercourse (UNAIDS, http://www.unaids.org/data/epi2010/). The options for prevention of HIV-infection are the abstinence or the use of condoms due to the lack of effective vaccine and therapy. Therefore, a good education and a preventive microbicide may represent the most promising strategy. Topical microbicides are products that can be applied to vaginal or rectal mucosa with the objective of attacking cellular or viral targets and to prevent, or at least significantly reduce, HIV transmission and the acquisition of HIV-infection. Microbicides may or may not be contraceptives and may or may not include strategies effective against sexually transmitted infections. At this moment, we have a better understanding of the invasion mechanisms that are used by HIV, the importance of HIV replication in target cells and the various host factors that restrict viral replication. However, an effective microbicide is not yet available; innovative approaches for the design of topical vaginal or rectal microbicides are urgently needed. The potential of the advancing field of dendrimers has been incorporated in the increasing efforts to address the major health problems of the developing world. In this review, advances in the design of innovative microbicides based on the use of dendrimers are presented.