Sex expression in the bitter gourd is mainly categorized into monoecious—staminate and pistillate flowers are produced separately in the same plant. Genes for its sex determination mechanism are quite important for genetic improvement through breeding, including the production of hybrid cultivars. In Cucurbitaceae, the mechanism of physiology and genetics of sex determination and expression in cucumber and melon have been extensively studied. For elucidating on sex determination in bitter gourd, a few gynoecious bitter gourd lines, showing only the female flowers, are found and employed as the maternal parent of F1 hybrid cultivars. Each of these gynoecious lines was predicted to be determined by a single recessive locus, which was genetically mapped. In monoecious bitter gourd, various ratios between female and male flowers per a plant (sex ratio) were observed and frequency of female flowers is an influential trait for the yield of fruits. By genetic mapping approaches, quantitative trait loci for female flower frequency were found. It was already well known that ethylene signaling is a key of sex determination in melon and cucumber, and causal genes for their sex determination were identified. According to bitter gourd draft genome sequences, putative orthologs of these sex determination genes could be identified. In other Momordica species, both monoecious and dioecious species were diverged. Genetic and genomic studies of sex determination in bitter gourd will greatly contribute to elucidate the evolution of monoecy and dioecy.