Selected aspects related to the mode of reactor operation and to the development of catalysts for the oxidative dehydrogenation of ethane and propane to their respective olefins are dealt with. The differences in the catalytic conversion when applying ethane or propane on rare-earth-oxide (REO)-based catalysts leading to the ignition of the reaction mixture are discussed. For ethane dehydrogenation, ethylene yields up to 46% were achieved by non-isothermal operation. Non-isothermicity was caused by ignition of the reaction and the resultant heat production. The formation of ethylene occurred via thermal pyrolysis and oxidative dehydrogenation. In general, autothermal operation looks promising for the production of ethylene from ethane. The advantage of REO-based catalysts as compared to noble metals like Pt is their high thermal stability. There are, however, limitations regarding the dehydrogenation of propane to propene in the autothermal mode. A high propene yield is not possible when applying such conditions since C-C scission results in a decrease of propene selectivity. The search for new active and selective formulations operating at low temperatures is, therefore, still timely. Against this requirement, special attention was given to a combinatorial and evolutionary approach for the selection and optimization of catalytic materials for the oxidative dehydrogenation of propane; selected experimental results as a proof of principle are presented.