Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy (cART) has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for chronic obstructive pulmonary disease, pulmonary hypertension, and lung cancer even in the era of cART. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggest that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage which predisposes PLWH to these conditions. Some of the factors which drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome towards pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH.