The deep lungs provide an efficient pathway for drugs to transport into the systemic circulation, as the extremely large surface area and thin epithelial membrane enable rapid drug transport to the blood stream. To penetrate into the deep lungs, aerosol particles with aerodynamic diameters of 1-3 µm are optimal. Large porous hollow particles (LPHPs) can achieve this aerodynamic size range through enhanced porosity within the particles (typically < 0.4 g/cm(3)), which aerodynamically balances the large particle size (> 5 µm, up to 30 µm). The physical properties of these particles provide some key advantages compared to their small, nonporous counterparts through enhanced dispersibility, efficient deep lung deposition, and avoidance of phagocytic clearance. This review highlights the potential of LPHPs in pulmonary delivery of systemic drugs, with a focus on their critical attributes and key formulation aspects. In addition, three examples of LPHPs under development are presented to emphasize the potential of this technology to treat systemic diseases.