This chapter focuses on the impact of optical clearing (OC) on skin autofluorescence (AF), i.e., on how the fluorescence emission spectral features and optical properties related to skin intrinsic fluorophores are more or less modified, enhanced or preserved during the clarification process. This chapter provides a review of research into the impact of OC agents (OCA) on skin AF emission features and describes some of the recent progress made in the analysis of OC-induced skin AF modifications using ex vivo and in vivo spectro-imaging modalities as well as related optical property modelling. First, the interest in exploiting AF-based in vivo optical biomarkers combined with OC approaches is discussed. Second, a short review of the main skin intrinsic fluorophores of interest and of the main mechanisms of OC in skin, as well as related OCAs, including chemical and physical enhancers, is presented. Finally, a review of the spectro-imaging techniques and modelling tools implemented in skin AF and OC studies is given, with a focus on skin AF spectroscopy.