The book was a commercial success but received mixed reviews due to questions about its scientific validity.

Brizendine's main thesis is that the human female brain is affected by the following hormones: estrogen, progesterone, testosterone, oxytocin, neurotransmitters (dopamine, serotonin), and that there are differences in the architecture of the brain (prefrontal cortex, hypothalamus, amygdala) that regulate such hormones and neurotransmitters.

The book also includes three appendices on hormone therapy, postpartum depression, and sexual orientation.

The book sold well but received mixed reviews because a number of journalists, popular science writers, and scientists questioned the validity of some of the content.

[8] The award cited errors in The Female Brain, including one sentence (removed from subsequent printings) which contrasted the number of words used by men and women in one day.