Clinicians frequently encounter patients with malignant and benign diseases involving the pleural space.Complications from these disease processes pose clinical challenges that often require a multi-disciplinary management approach. Here we discuss therapeutic options available for complicated diseases of the pleural space, including loculated malignant effusions, complicated pleural infections, hemothorax, nonexpanding lung, pleural thickening, and persistent bronchopleural fistulas. Our objective is to review current literature on management of these complex issues.