In the present study, five detailed reaction mechanisms have been employed for simulating 530 ignition delay times involving mixtures containing methane, hydrogen, carbon monoxide and carbon dioxide. A novel concept, Reaction Significance Analysis (RSA), has been used for identifying those kinetic parameters which have the greatest influence on the disparities between a given set of experimental data and the model predictions. Overall, most mechanisms capture at best the combustion of biogas and display their poorest performance in relation to the combustion of bio-syngas. NUIG (a reaction mechanism developed at the National University of Ireland, Galway) proves to be the best choice for simulating the burning of bio-syngas, its imperfection notwithstanding. Generally, models tend to over-predict ignition delay times measured at the lowest temperatures. This effect is mostly related to the inhomogeneous behaviour of shock tubes under those conditions. Besides that, Reaction Significance Analyses revealed a correlation between poor modelling performance and reactions belonging to the subsystem HO2–H2O2. We identified situations where such chemical kinetic factors appear to play a role in inaccurate predictions. Overall, the present study strongly indicates that the kinetic modelling of the combustion of CH4–CO–H2–CO2 should not be seen as a problem successfully solved in the past once and for all. There is a genuine need for more kinetic experiments targeting reaction parameters which remain widely uncertain owing to their weak influence on most available measurements.