Vaginal contraception, the oldest method of fertility regulation that remained virtually forgotten for a few decades has recently come under focal review due to an increase in STDs and HIV infections worldwide. Today it is being considered very strongly that a conceptual microbicidal spermicide can tender protection against pregnancy as well as STDs (including AIDS), simultaneously. However the two activities (spermicidal and microbicidal) need to be integrated in vaginal preparations, as many women across the world may be concerned more about the unwanted pregnancy rather than the STI during a coital act. A strong detergent like nonoxynol-9 (N-9) has been used as a spermicide in many local contraceptive preparations and studies have shown that it also exhibits significant microbicidal activity in vitro. However, recent clinical trials have shown that detergent spermicides do not provide any protection against STDs and AIDS but may in fact even promote their transmission. This anomaly has largely been attributed to their surfactant nature that irritates the vagina and kills the normal vaginal flora making it more susceptible to STD infections. An urgent need for a suitable non-detergent spermicide has thus emerged to replace N-9 in local contraceptive preparations. Anticipating the potential of spermicide-based vaginal contraceptives in the reproductive health of women, a large number of synthetic, non-detergent molecules were designed and evaluated at this Institute over recent years. Simultaneously, a number of natural products from terrestrial plants and marine flora/fauna were also evaluated for spermicidal activity. A local contraceptive preparation incorporating the active ingredient from the fruit pericarp of Sapindus mukorossi has successfully completed Phase III clinical trials in India and is ready for marketing. Recent studies have indicated that in comparison to N-9, this ingredient is much less toxic to Lactobacillus spp. and effectively inhibits the growth of Trichomonas vaginalis in vitro. Other candidate spermicides/microbicides under development worldwide have been reviewed briefly.