Generalized two-dimensional correlation spectroscopy (2D COS) is a modern analytical tool that is increasingly being used in the interpretation of complex spectra that have broad, multiply overlapped spectral features. Besides functioning as a spectral resolution-enhancement tool similar to curve-fitting or deconvolution, 2D COS possesses an additional advantage in that it is capable of discerning temporal relationships between intensity variations within a set of spectra. Infrared reflection-absorbance spectroscopy (IRRAS) at the air-water interface has been a very useful technique in studying the structure of biologically relevant molecules and the interaction between components of biological membranes in an environment close to what is found in nature. To better understand interfacial bio-mimetic structure, 2D COS can be applied to the IRRAS spectra to analyze changes in infrared intensities as a function of an environmental perturbation such as a change in temperature or surface pressure. To overcome some of the inherent limitations of the generalized 2D method, model-based approaches such as βν- and kν-correlation analyses and the global 2D phase angle method were developed. This review discusses some of the recent applications of these novel methods to Langmuir monolayers of phospholipids and proteins at the air-water interface and Langmuir-Blodgett polymer films. Copyright © 2006 John Wiley & Sons, Ltd.