The preferential oxidation of CO (PROX) on hydrogen rich streams has been studied using Pt-based and Pt-free catalysts. A combination of spectroscopic techniques is used to characterize the studied catalysts such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), X-ray absorption fine structure (EXAFS), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). A Monte Carlo method is proposed to deal with stiff reaction mechanisms, and it is used to simulate the PROX reaction on Pt. The experimental results indicate that when a Pt/Al2O3 catalyst is promoted with small amounts of Nb, the activity on the PROX reaction is improved. In contrast, on a Ptb2O5 catalyst the CO oxidation is strongly inhibited. The latter catalyst shows resistant to CO poisoning since it maintains high activity on hydrogen oxidation. It was found that the Nb promoted Pt-catalysts stabilize Pt+2 and it remains stable after reduction treatments and under reaction condition. Infrared results show that Pt+2 species are still able to adsorb CO. It was found that surface carbonate-like species are a function of surface hydroxyls. The most active Nb-promoted catalysts show the highest absorbance of carbonate-like species. Kinetics results suggest that the formation of carbonate-like species restrict the hydrogen spillover mechanism. A new Kinetic Monte Carlo approach (log-KMC) has been introduced which allows solving reaction systems with high degree of stiffness. The simulations of the PROX reaction show that the decrease in Pt dispersion leads to the decrease in less active corner sites. As the crystallite size increases, the population of more active (111) face sites also increases leading to more active catalysts. In addition, it was found that oxygen adsorption is the rate limiting step in the PROX reaction. The PROX reaction on Pt-free metal oxides shows that when copper is supported on TiO2 nanotubes, the activity to CO oxidation is similar to that of Pt-based catalysts. Copper is finely dispersed when supported on TiO2 nanotubes and it is present as a mixture of both Cu+1 and Cu+2. The rate of transformation of the copper oxidation states follows the expression: r=k[Cu+2][Cu+1]-1 .