Sexual transmission via vaginal intercourse accounts for majority of human immunodeficiency virus type 1 (HIV-1) in women. The mechanism by which HIV-1 traverses the tightly bound tissue structure of cervical/vaginal epithelium, especially when vaginal/cervical epithelial cells do not express HIV-1 receptor or co-receptors is still unknown. With the restrictions on studying these mechanisms in humans and the substantial anatomical differences between human and non-human primates, investigators have used cervical tissue-derived organ culture models that closely mimic the human in vivo environment to study HIV-1 transmission. This report reviews our current knowledge of various cervical tissue-derived organ cultures and their application in studying HIV-1 transmission and microbicide development.