The oxygen electro-reduction reaction (ORR) is the cathode reaction in fuel cells, envisioned to replace combustion engines for transportation [1]. The first commercial vehicles powered by acidic-type H2/air polymer-electrolyte-membrane fuel cells were released in 2015. The ORR being particularly sluggish, research on novel ORR catalysts is unabated since the 1990's. While novel Pt nanostructures and concepts have allowed decreasing the amount of precious metal [2-3], recent advances in the class of iron-nitrogen-carbon (Fe-N-C) catalysts have attracted attention [4-5]. Their development was initially inspired by macromolecules with an FeN4 core, catalyzing ORR in the respiratory system of living organisms. Synthesized at ³ 700 °C, modern Fe-N-C catalysts obtained via the pyrolysis of catalyst precursors prepared from separate precursors of the metal, nitrogen and carbon elements are the object of intense research regarding the nature, the structure and the stability of their active sites [6-7]. Improved power performance in air-fed polymer-electrolyte fuel cells along with improved durability of Me-N-C catalysts in acidic conditions are the next key practical challenges. This presentation will focus on novel characterisation tools under development to investigate the active-site structure in Fe-N-C catalysts in ex situ and also in operando conditions during active-site formation (at elevated temperature) or during active-site operation (in electrochemical conditions). Gas-phase and liquid-phase techniques under development to i) quantify the total number of electrochemically-accessible FeNx active sites and ii) distinguish different types of FeNx moieties according to their binding of targeted adsorbates will also be discussed [8-10]. Recent practical approaches to increase the site density (site utilization) and to favor the location of FeNx moieties on the electrochemical interface will be discussed, in the light of those techniques. Acknowledgement: The research leading to these results has received funding from FCH2 JU under grant agreement 779366, CRESCENDO. References T. Wagner, B. Lakshmanan and M.F. Matthias, J. P. Chem. Lett. 1, 2204 (2010). K. Debe, Nature 486, 43 (2012).Chattot et al, Nat. Mater. 17, 827 (2018)Jaouen, E. Proietti, M. Lefèvre, R. Chenitz, J.P. Dodelet, G. Wu, H.T. Chung, C.M. Johnston, P. Zelenay, Energy Environ. Sci . 4, 114 (2011).Shui, C. Chen, L. Grabstanowicz D. Zhao, D.J. Liu, Proc. Nat. Acad. Sci. 112, 10629 (2015)Zitolo, V. Goellner, V. Armel, M-T. Sougrati, T. Mineva, L. Stievano, E. Fonda and F. Jaouen, Nature Mater. 14, 937 (2015 ).H Choi, C. Baldizzone, J-P. Grote, Anna K. Schuppert, F. Jaouen and K. Mayrhofer, Angew. Chemie Int. Ed. 54, 12753 (2015). Malko, A. Kucernak, and T. Lopes, Nature Communications, 7 13285 (2016).R. Sahraie, U. I. Kramm, J. Steinberg, Y. Zhang, A. Thomas, T. Reier, J.-P. Paraknowitsch, and P. Strasser, Nature Communications, 6, 8618 (2015).M-W. Chung, G. Chon, H. Kim, F. Jaouen, C.H. Choi, ChemElectroChem 5, 1880 (2018)