Research with both coal substructure model compounds and macromolecular coal has shown that intermonomeric chemical bonds within coal are susceptible to cleavage by microbial enzymes from bacterial and fungal sources. This is particularly true when low rank lignite coals are used as substrates for enzymes after first being solubilized under alkaline conditions to form water-soluble coal polymers. When these soluble polymers are used as substrates, high-performance liquid chromatography (HPLC) methods are used to show that particular enzymes catalyze their depolymerization. By using chemical presolubilization followed by enzymatic depolymerization, it may be possible to develop commercial processes for the enzymatic depolymerization of coal into useful low-mol-wt chemicals, or into liquid or gaseous fuels. Evidence indicates that oxidative enzymes, such as peroxidases or etherases, and hydrolytic enzymes, such as esterases, have the best potential for effectively depolymerizing coal. Recent findings in our laboratory also suggest that certain hydrolases from saprophytic soil fungi may also work well.