Pneumothorax is defined as the presence of air in the pleural cavity. Spontaneous pneumothorax, occurring without antecedent traumatic or iatrogenic cause, is sub-divided into primary and secondary. The severity of pneumothorax could be varied from asymptomatic to hemodynamically compromised. Optimal management of this benign disease has been a matter of debate. In addition to evacuating air from the pleural space by simple aspiration or chest tube drainage, the management of spontaneous pneumothorax also focused on ceasing air leakage and preventing recurrences by surgical intervention or chemical pleurodesis. Chemical pleurodesis is a procedure to achieve symphysis between the two layers of pleura by sclerosing agents. In the current practice guidelines, chemical pleurodesis is reserved for patients unable or unwilling to receive surgery. Recent researches have found that chemical pleurodesis is also safe and effective in preventing pneumothorax recurrence in patients with the first episode of spontaneous pneumothorax or after thoracoscopic surgery and treating persistent air leakage after thoracoscopic surgery. In this article we aimed at exploring the role of chemical pleurodesis for spontaneous pneumothorax, including ceasing air leakage and preventing recurrence. The indications, choice of sclerosants, safety, effects, and possible side effects or complications of chemical pleurodesis are also reviewed here.