Even in the high-pressure limit, it is not hard to identify important systems where there are so many possible reactions and reactive intermediates that it would be difficult-to-impossible to consider them all. A key practical limitation is that today's differential equation solvers run into numerical difficulties for systems with more than about 10,000 stiff non-linear differential equations (i.e. more than about 10,000 distinct radicals), due to round-off issues solving equations involving the large ill-conditioned Jacobian matrices. But some common mixtures, e.g. diesel fuel, contain more than 10,000 distinct stable molecules, and form more than 100,000 different radicals when they burn. As another example, pyrolysis of biomass or waste polymers involves thousands of distinct radicals from H-abstractions of every C-H bond in the macromolecules, and each of these can react to form several different oligomers and product radicals. As the reactions proceed, multiple sites on the polymer are functionalized, leading to a combinatorial explosion of isomers. Similarly challenging are systems where polymerization or soot formation is occurring, since a detailed model would need to include multiple reactive intermediates of almost every size between the starting material and the macromolecules being formed.