Spontaneous pneumothorax (SP) secondary to the acquired immunodeficiency syndrome (AIDS) emerged in the decade of the 1980s. It has become an increasingly difficult condition to treat successfully both for the pulmonary internist and the surgeon. AIDS-related SP is complicated by a virulent form of necrotizing subpleural necrosis that results in diffuse air leaks that are refractory to the standard, traditional forms of therapy which enjoy good success for SP related to classic subpleural bleb disease. AIDS-related SP carries a high mortality rate despite treatment, independent of the development of primary respiratory failure. In reviewing our experience of 46 patients from a single institution treated over the past 10 years, we found that due to the high primary and secondary treatment failure rates, an aggressive stepped-care management of large-bore intercostal tube drainage, chemical pleurodesis, and early video-assisted talc poudrage is recommended in an attempt to shorten the duration of hospital stay, hospital costs, and mortality.