Patients with a pleural effusion can suffer from many symptoms including breathlessness. The pathophysiological effects of pleural effusions on the cardiorespiratory system are complex. The mechanisms of breathlessness associated with an effusion are poorly understood, and improvements in breathlessness following therapeutic drainage of the effusion can be variable. This chapter reviews the current literature on common symptoms and pathophysiological effects associated with pleural effusions, the mechanisms underlying breathlessness in effusions and the response to pleural drainage, and symptom measurement tools and predictors of benefit following drainage. It highlights current research, knowledge gaps and future directions in this area.