The photoplethysmographic waveform sits at the core of the most used, and arguably the most important, clinical monitor, the pulse oximeter. Interestingly, the pulse oximeter was discovered while examining an artifact during the development of a noninvasive cardiac output monitor. This article will explore the response of the pulse oximeter waveform to various modes of ventilation. Modern digital signal processing is allowing for a re-examination of this ubiquitous signal. The effect of ventilation on the photoplethysmographic waveform has long been thought of as a source of artifact. The primary goal of this article is to improve the understanding of the underlying physiology responsible for the observed phenomena, thereby encouraging the utilization of this understanding to develop new methods of patient monitoring. The reader will be presented with a review of respiratory physiology followed by numerous examples of the impact of ventilation on the photoplethysmographic waveform.