Management of MPE is a problem now receiving considerable attention compared with historical precedent. Although the quality of investigation focused on MPE has improved with more prospective randomized trials published in the past 10 years than the prior 70, the optimal approach for MPE treatment remains unclear. Our recommendation fits with the current theme of personalized medicine that permeates thoracic oncology practice today. Multiple options from large- and small-bore tube pleurodesis to multiple sclerosants, indwelling pleural catheters, and thoracoscopy are available. Treatment strategies should consider and address performance status, survival expectations, extent of dyspnea, quality of life, availability of social supports, cost, and patient preference. The literature does not support any one approach as optimal. Further well-designed studies will be crucial to define best practices, create appropriate treatment algorithms, and where possible, standardize care for this difficult problem.