A quarter century old and still going strong, the HIV/AIDS pandemic is already the deadliest and longest lasting plague in mankind's recorded history. Reportedly among the weakest of the viruses, HIV's survival instincts have relied on extreme adaptability at the molecular and virologic levels on its part. In addition, it has preyed on certain prevalent weaknesses on the part of its host (human society) - extreme poverty; gender bias; lack of education and high prevalence of STIs- to prolong its lethal grip on humanity for as long as possible. This astounding adaptability is evident by the tremendous geographic, gender, mode of transmission and age shifts it has displayed over its now respectably long history. From localized epidemics in localities in the developed world at its onset, it has gravitated and now firmly entrenched itself selecting Sub-Saharan Africa as the epicenter of its global scourge. From a disease of men having sex with men (MSMs) at its inception, it has undergone a gender shift with a definite and alarming "feminization'" or as Kofi Annan put it, has the "Face of a woman". From a demonstrable prevalence, concentrating in adults, it has chillingly shifted to being an infection that affects predominantly younger age groups and adolescents. And from its early homosexual and injection drug use transmission modes it has shifted to a predominantly heterosexual transmission for the majority of new infections. Behavioral modifications (health education towards safe sexual practices and VCT provision and utilization); correct and consistent use of male and female condoms; control of sexually transmitted diseases and strategies to prevent mother to child transmission (PMTCT) are effective methods of HIV/AIDS prevention. Their effectiveness has been demonstrated by their ability to contain the epidemic in countries that have successfully implemented them. Of questionable value in prevention but gaining momentum in accumulating data proving their effectiveness in HIV prevention are strategies including male circumcision; PEP (post-exposure prophylaxis); PREP (pre-exposure prophylaxis) and provision of ante-retroviral therapy to all who are in need. Experiences in prevention efforts in resource-poor settings over the last two decades have indicated that the traditional ABC model (abstinence, being faithful to one's partner and condom use) are inadequate in controlling HIV in those settings. Well-known biologic vulnerabilities in women as well as socio-economic, cultural and gender bias towards women, stand in the way of effective implementation of the available prevention strategies. It has become increasingly evident that as part of a comprehensive HIV prevention strategy, a female-controlled method of prevention is crucial for the eventual control of the epidemic in Africa. To this end, efforts to develop a "microbicide"- a topical agent that can be applied vaginally by women to protect themselves from infection; and a product that they can use without the necessary consent of their partner - have been gathering momentum over the last decade. At present, nearly sixty potential microbicides are in the development pipeline. Of these six are in the last (phase III) effectiveness trials that precede drug licensing. There is a general belief in the scientific community that an effective microbicidal agent for HIV prevention might be available in the next five to seven years. Lack of finance and ethical issues in conducting research are delaying rapid development of an effective agent. Ethiopia has been largely left out of research efforts towards microbicides development. It is essential that cognizance of this emerging HIV prevention strategy by health care professionals and the general public be developed in order to avoid undue delays in effective utilization once an effective agent becomes part of our HIV prevention arsenal.