Time-Of-Flight Secondary Ion Mass Spectrometry is compared to other mass spectrometry imaging techniques, and recent improvements of the experimental methods, driven by biological and biomedical applications, are described and discussed. This review shows that this method that can be considered as a micrometric molecular histology is particularly efficient for obtaining images of various lipid species at the surface of a tissue sample, without sample preparation, and with a routine spatial resolution of 1μm or less.