Optical spectroscopy is widely used for quantitative detection of small molecules in complex gas matrices. Employing a laser as a light source enables highly sensitive, selective, and accurate trace gas analysis in exhaled breath without the need for frequent calibration. Many volatile species with direct physiological relevance, especially small molecules such as CO2, CO, NO, CH4, NH3, HCN, C2H4, and their isotopoloques, can be measured with high time resolution using compact optical analyzers. Thus, laser-based sensors are an important complement to other analytical platforms and contribute to establishing breath gas analysis in the clinical practice. This chapter introduces the basics of optical spectroscopy and describes the most relevant techniques currently used in the field, such as nondispersive, laser absorption, and photoacoustic spectroscopy. Successful applications of optical methods are presented, and the future prospects are discussed. Owing to the advent of novel light sources, such as quantum cascade lasers and optical frequency combs, spectroscopy will continue to play a significant role in breath gas analysis.