Major depression is frequently associated with sexual dysfunction (over 70% of patients), and the antidepressant medications used to treat the illness may exacerbate pre-existing sexual dysfunction, or induce sexual dysfunction not present on diagnosis. In women, sex hormones that change across the life cycle, menstrual cycle, and diurnally have direct effects on sexual functioning, and indirect effects via modulation of neurotransmitter systems. These complex neuroendocrine effects lead to the sexual dysfunction seen with antidepressants. Strategies to manage these effects have had some success. They include switching to antidepressants with minimal sexual side effects, addition of hormones and/or antidotes, and lowering the dose of medication. Emerging data on the pathophysiology of sexual function and dysfunction, and new treatment options may lead to improved quality of life for women diagnosed with depression.