Lithium-oxygen (Li-O2) batteries have been intensively investigated in recent decades for their utilization in electric vehicles. The intrinsic challenges arising from O2 (electro)- chemistry have been mitigated by developing various types of catalysts, porous electrode materials, and stable electrolyte solutions. At the next stage, we face the need to reform batteries by substituting pure O2 gas with air from Earth's atmosphere. Thus, the key emerging challenges of Li-air batteries, which are related to the selective filtration of O2 gas from air and the suppression of undesired reactions with other constituents in air, such as N2, water vapor (H2O), and carbon dioxide (CO2), should be properly addressed. In this review, we discuss all key aspects for developing Li-air batteries that are optimized for operating in ambient air and highlight the crucial considerations and perspectives for future air-breathing batteries.