Study Objective To describe features of menstruation, menstrual-related symptoms, and menstrual management in females with Rett syndrome (RTT) to help develop a clinical approach to these parameters in RTT. Design Retrospective cross-sectional chart review and prospective survey. Setting Cincinnati Children's Hospital Medical Center, Rett Syndrome and Related Spectrum Disorders Clinic. Participants Females with RTT (12-55 years of age) and their caregivers. Main Outcome Measures Descriptive data on features of menstruation and menstrual-related symptoms in individuals with Rett syndrome; prevalence, types, reason for use/discontinuation, and efficacy of hormonal treatment in females with RTT. Results Age at menarche, menstrual cycle length, and menstrual period length in females with RTT are comparable to those in typically developing females and females with other neurodevelopmental disabilities. Dysmenorrhea and emotional lability are common menstrual cycle−related changes among females with RTT; 22.1% of participants also reported catamenial seizures. Oral progestin, combined oral contraceptive pill, and depot-medroxyprogesterone acetate (DMPA) were effectively used to suppress or regulate menstruation and to manage menstrual-related symptoms. Conclusions Characteristics of menstruation in females with RTT are comparable to those of typically developing females, with the exception of increase in catamenial seizure activity. Hormonal treatments are used for management of menstruation, dysmenorrhea, and seizures. Choice of hormonal treatment is influenced by bone health and immobility in females with RTT.