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Pleural infection remains a common problem with significant associated morbidity and mortality. The current treatment paradigm for pleural infection appears to be shifting as more recent data have suggested that the use of intrapleural fibrinolytic therapy (IPFT) may be adequate for treatment, potentially avoiding the need for surgical intervention in a significant number of patients.The previous Multicenter Intrapleural Sepsis Trial demonstrated improved outcomes when utilizing combined IPFT, however, more recently alterations in this dosing regimen have been explored. Successful retrospective studies have examined the role of extended dosing (more than six sequential doses), concurrent dosing (instilling both medications together as opposed to separate medication dwell times), and daily dosing of intrapleural medications.Although the use of IPFT is likely shifting the management of pleural infection to less surgical intervention, the optimal dosing strategy of intrapleural therapy remains undefined. Within the last few years more data on variations of IPFT have emerged. This data remains of lower quality because of its retrospective nature and future prospective evaluation is required to further define the optimal dosing regimen for IPFT in complicated pleural space infections.