The gonadal primordium is the only tissue in mammals that has two divergent developmental fates leading ultimately to the formation of either a testis or an ovary. The goal of this review is to summarize the major characteristics of the male and female transcriptional programs triggered in the developing mouse gonads during the critical time window of sex determination. Expression profiling studies reveal that both male and female genetic programs are initiated as early as embryonic day (E) 11.5. By E13.5, more than 1000 genes are overexpressed either in developing ovaries or testes. A large fraction of these have so far no known roles during gonadal differentiation, yet interestingly some of their human orthologues map to chromosomal loci associated with sexual disorders. Identifying the functional roles for these candidate genes will improve our understanding of sex determination and provide new insights into the causes of gonadal dysgenesis and reproductive disorders.