Obstructive sleep apnea (OSA) is a common disease that is often under-diagnosed and under-treated in all ages. This is due to differences in morphology, diversity in clinical phenotypes, and differences in diagnosis and treatment of OSA in children and adults, even among individuals of the same age. Therefore, a personalized medicine approach to diagnosis and treatment of OSA is necessary for physicians in clinical practice. In children and adults without serious underlying medical conditions, polysomnography at sleep labs may be an inappropriate and inconvenient testing modality compared to home sleep apnea testing. In addition, the apnea–hypopnea index should not be considered as a single parameter for making treatment decisions. Thus, the treatment of OSA should be personalized and based on individual tolerance to sleep-quality-related parameters measured by the microarousal index, harmful effects of OSA on the cardiovascular system related to severe hypoxia, and patients’ comorbidities. The current treatment options for OSA include lifestyle modification, continuous positive airway pressure (CPAP) therapy, oral appliance, surgery, and other alternative treatments. CPAP therapy has been recommended as a cornerstone treatment for moderate-to-severe OSA in adults. However, not all patients can afford or tolerate CPAP therapy. This narrative review seeks to describe the current concepts and relevant approaches towards personalized management of patients with OSA, according to pathophysiology, cluster analysis of clinical characteristics, adequate combined therapy, and the consideration of patients’ expectations.