The pathogenesis of obstructive sleep apnea (OSA) has undergone major revisions since it was first described in 1978. This article focuses on new advances. Although it is still necessary to have a collapsible airway to develop OSA, it is primarily the response to obstruction that determines OSA severity and clinical presentation. Identifying factors that determine whether the response is stable or unstable through phenotyping is a promising approach that may lead to pharmacologic therapy in selected patients.