Owing to the sensitivity of Static SIMS to molecular structures and its selectivity to the outermost surface layers, this technique is very well suited to gain information about conformation and orientation of molecules at the surface. The aim of this presentation is to discuss critically and to illustrate these unique features of Static SIMS with selected applications. Firstly, the SIMS information depth and its dependence on the molecular fragment ion size are presented in order to justify the surface selectivity. This has been experimentally determined by looking at the substrate signal attenuation when depositing organic layers in a controlled manner on different materials as was done with Langmuir-Blodgett layers and polyelectrolyte ultra thin films. As illustrated for polymers, the surface selectivity allowed SIMS to be sensitive to tacticity of macrochains and orientation of mobile pendant groups. Based on these performances, Static SIMS has been used to study protein adsorption and highlighted modifications in protein conformation/orientation, depending on the substrate properties. Finally, the limitations of Static SIMS analyses are discussed. Indeed, for sample surfaces non-uniform at a nanoscale, which is beyond the limits of SIMS imaging, the chemical molecular information cannot be sufficient. It has to be complemented by surface morphology information in order to get a correct view of the system. This is illustrated by our recent study of very thin layers of block copolymers and polymer blends, forming nanostructures at the surface. (c) 2006 Elsevier B.V. All rights reserved.