The fouling of catalysts for the upgrading of bio-oils appears to be very different from the fouling of catalysts for the hydroprocessing of petroleum-derived streams. There are two reasons for the differences: (a) bio-oil contains polarizable components and phases that can stabilize reaction intermediates exhibiting charge separation and (b) bio-oil components contain functional groups that contain O, notably carbonyls (>C-O). Aldol condensation of carbonyls affords very different pathways for the production of oligomeric, refractory deposits than does dehydrogenation/polymerization of petroleum-derived hydrocarbons. Colloquially, we refer to the bio-oil-derived deposits as gunk to discriminate them from coke, the carbonaceous deposits encountered in petroleum refining. Classical gelation appears to be a suitable model for the gunking reaction. Our work has helped explain the temperature range at which bio-oil should be preprocessed (stabilized) to confer longer lifetimes on the catalysts used for more severe processing. Stochastic modeling (kinetic Monte Carlo simulations) appears promising to capture the rates of oligomerization of bio-oil.