Platinum single crystals decorated with noble metal nanoislands have found increasing applications as model systems for highly active fuel cell catalysis due to their enhanced electrocatalytic properties. Pt single crystals modified with Ru nanoislands were particularly explored due to the high catalytic efficiency of PtRu bimetallic electrodes with respect to the removal of CO poisoning during methanol oxidation. The precise geometry of the Ru-modified Pt single crystals, acquired by the use of both ex situ and in situ scanning tunneling microscopy (STM) techniques, enabled fundamental investigations of their activity from the structural perspective. Comprehensive in situ STM studies of Au single crystals decorated with Ru nanoislands were also undertaken in order to elucidate the catalytic behavior of ruthenium nanoislands, since the Au substrate alone was much less active towards CO adsorption or oxidation.