Thoracentesis should be conducted for new and unexplained pleural effusions, with the fluid characteristics indicating possible conditions such as empyema or hemothorax. Light's criteria help differentiate between exudative and transudative effusions, though misclassification can occur in certain conditions, necessitating additional tests like serum-effusion gradients. Factors like pleural fluid glucose, pH, and cytology are vital in diagnosing conditions like tuberculosis and malignancies.