The effect of hormone therapy on sleep-disordered breathing in transgender patients has not been described. We present three cases of patients undergoing gender reassignment and treated with hormone replacement. The first case was a transgender woman (assigned male at birth) with a prolonged history of severe obstructive sleep apnea (OSA) that resolved following initiation of female sex hormones. The second and third cases both address transgender males (assigned female at birth) in whom OSA developed following initiation of male sex hormones (with pretreatment polysomnography documenting absence of OSA). The growing interest in transgender health warrants further evaluation of the effects of related therapies on sleep and sleep-disordered breathing.