The pulse oximetry plethysmographic signal resembles the peripheral arterial pressure waveform, and the degree of respiratory variation in the pulse oximetry wave is close to the degree of respiratory arterial pulse pressure variation. Thus, it is tempting to speculate that pulse oximetry can be used to assess preload responsiveness in mechanically ventilated patients. In this commentary we briefly review the complex meaning of the pulse oximetry plethysmographic signal and highlight the advantages, limitations and pitfalls of the pulse oximetry method. Future studies including volume challenge must be performed to test whether the pulse oximetry waveform can really serve as a nonivasive tool for the guidance of fluid therapy in patients receiving mechanical ventilation in intensive care units and in operating rooms.