Time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) offers the prospect of in situ and instantaneous diagnosis of atherosclerotic lesions. This chapter provides an overview of this important area of research. The introduction describes elements of the pathology, the role in clinical applications, and an introduction to the method. Subsequent sections detail progress in the experimental work, analysis of data, roles of specific endogenous fluorophores, and the current status of experiments and their interpretation.