Management of malignant pleural effusion is a medical challenge, and several methods have been proposed to deal with it including thoracentesis, indwelling pleural catheter placement, and chemical or mechanical pleurodesis. Each method, however, has its advantages and disadvantages. Talc pleurodesis is generally recognized as the most effective and safest method for the induction of chemical pleurodesis. However, in rare cases, it can lead to acute respiratory distress syndrome (ARDS). In this article, we report the case of a patient with metastatic adenocarcinoma to the pleura who presents with shortness of breath and malignant pleural effusion, develops ARDS after pleurodesis with talc, and expires despite the partial improvement of lung involvement. The symptoms and causes of this rare side effect as well as the methods that can be used to deal with it are reviewed in this article.