Skin autofluorescence was observed as early as 1908. Its applications in dermatology was first reported in 1925- the use of Wood's lamp for the detection of fungal infection. In the first part of the paper, a historical review was presented on skin autofluorescence properties. In the second part, systematic research done in out laboratory on autofluorescence properties of normal and diseased skin was summarized. We developed three tools for the study: 1) a compact fiber optic spectrometer for in vivo macroscopic fluorescence spectral measurements on volunteers and patients; 2) a CCD camera based fluorescence imaging for in vivo macroscopic imaging of 2D fluorescence intensity distributions over various skin diseases; 3) a fiber optic microspectrophotometer (MSP) system for in vitro microscopic fluorescence spectral measurements and fluorescence imaging of frozen tissue sections. With these tools, we obtained the excitation-emission matrices (EEMs) of in vivo normal skin, the temporal dynamics of skin autofluorescence decay under continuous wave laser exposure, and fluorescence spectra of 1500 lesions from 600 patients spanning 35 disease types. Monte Carlo simulation has been employed to explain the autofluorescence decay dynamics and to reconstruct the in vivo spectra from in vitro microscopic fluorophore distribution and intrinsic fluorescence spectra of various skin structures. Spectral feature based linear discrimination function analysis and principal components decomposition analysis are performed to assess the potential of autofluorescence spectroscopy for skin cancer detection. Clinical test of a fluorescence scope system for skin cancer margin delineation is under way.© (2000) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.