Pleural Effusion (PE) is a common clinical condition, which can greatly affect patients’ quality of life. Etiology of PEs can be variable, although in over 70% of cases they prove to be malignant in nature. Video-Assisted Thoracoscopic Surgery (VATS) is now routinely employed for management of recurrent PE and allows a thorough exploration of the pleural cavity, accomplishment of gross multiple biopsies and, whenever required, pleurodesis to prevent recurrences. VATS is usually performed under general anesthesia although this type of anesthesia can be associated with several adverse effects, particularly in the presence of comorbidities such as advanced malignancy, cardiopathy and severe systemic diseases. For this reason, use of local anesthesia in spontaneously ventilating patients has been advocated and we also started a clinical program of VATS carried out through local or Thoracic Epidural Anesthesia (TEA) in fully awake, spontaneously ventilating patients. Awake VATS management of PE requires a single trocar access; it is easily performed and results in optimal patients tolerability, minimal hospitalization and satisfactory outcome.