PURPOSE OF REVIEW: Management of pleural infection remains heterogeneous worldwide. This review highlights current controversies in therapeutic strategies for pleural infection, focusing particularly on recent studies and their implications. RECENT FINDINGS: The introduction of intrapleural therapy combining alteplase [a tissue plasminogen activator (tPA)] and deoxyribonuclease (DNase) has revolutionized treatment practices, though the optimal delivery and dosing regimen is an area of active investigation. Variations to simplify administration protocols and/or to lower the required drug doses have been published. Most were exploratory studies, but the variations showed maintained therapeutic efficacy.Whether intrapleural alteplase/DNase or video-assisted thoracoscopic surgery (VATS) is superior is a topic of debate. Retrospective comparative analyses between the two revealed no clear benefits on all-cause mortality from either approach. Pilot randomized trials have been published and further full-scale, head-to-head trials are underway. SUMMARY: Effective management of pleural infection involves adequate pleural drainage and appropriate antibiotic use. This review outlines the current evidence (and its limitations) and highlights knowledge gaps in optimizing the therapeutic strategies.