Asthma and obstructive sleep apnea (OSA) are among the most prevalent chronic human diseases of the 21st century. They share several risk and aggravating factors such as obesity, smoking, gastroesophageal reflux, sinonasal disease or upper airway involvement, systemic inflammation, etc. Although the association between OSA and chronic obstructive pulmonary disease or “overlap syndrome” is better known and characterized, the association of asthma and OSA or “alternative overlap syndrome” is less clearly defined and understood. Nevertheless, their coexistence has synergistic effects on patient symptoms, response to therapy, and general outcomes. Taxonomically, asthma and OSA are syndromically defined entities that are quite heterogeneous, being characterized by a plethora of clinical phenotypes. The complex interactions between these conditions should take into account more specific etiopathogenic mechanisms or distinct disease endotypes. The potential clinical, pathogenic, and therapeutic significance of the disease endotypes is still emerging and needs further evaluation. We present here a review on the bidirectional relationships between asthma and OSA, including their clinical, pathophysiologic, and therapeutic connections. Furthermore, we propose here to look at these interactions beyond the development of comprehensive inventories of genotypes, clinical and pathophysiologic phenotypes, but in the larger context of obstructive lung and airway disorders, with the goal to reassess meaningful syndromes based on natural history and predictable patient outcomes, which will help us better stratify therapy in an era of personalized medicine.