The authors describe a 42-year-old woman with previously normal sexual function who gradually developed loss of libido during treatment with esomeprazole. While taking esomeprazole, the patient's loss of libido improved with oral testosterone supplementation and deteriorated after testosterone withdrawal. There was steady improvement in both sexual function and serum free testosterone concentration after discontinuation of esomeprazole. Due to the temporal relationship between esomeprazole intake and sexual dysfunction, the authors postulate that esomeprazole causes induction of testosterone metabolism. The authors believe this to be the first case of female sexual dysfunction associated with esomeprazole described in the literature. They discuss a number of possible mechanisms for this effect.