Experimental data gathered over the past several years show that the interactions of microorganisms with crude oils are variable and depend on the microbial species and the chemical composition of crude oils. Systematic studies of chemical mechanisms by which selected microorganisms react with crude oils have led to the identification of biochemical markers characteristic of the interactions of microbes with oils. These biomarkers belong to several groups of natural products ranging from saturate and polyaromatic hydrocarbons containing heterocyclics to organometallic compounds. Chemical marker analyses indicate that the interaction of microbes with crude oils involves multiple chemical reactions resulting from the biochemical interactions between microbes and oils. Different interactions may influence the efficiency of processes in which single or mixed microbial species are used for the oil treatment and may also suggest possible combinations of biological and chemical technologies. Further, the biochemical conversions of oils can be monitored by these chemical markers, which is particularly useful in the optimization of biochemical processing, cost efficiency, and engineering studies. Recent results from these studies will be discussed.