Bacillus methanolicus is a Gram-positive, restricted facultative, aerobic methylotroph capable of growing on methanol as sole carbon source at temperatures between 35 and 60 °C. Wild-type strains of B. methanolicus growing on methanol have been reported to secrete 58 g/l of L-glutamate in fed-batch cultures while classical mutants can secrete 37 g/l of L-lysine, at 50 °C. Production of recombinant proteins by B.methanolicus at 50 °C has been demonstrated. Methanol is converted to formaldehyde (FA) by methanol dehydrogenase (mdh). FA is either assimilated into biomass via the ribulose monophosphate (RuMP) pathway or dissimilated by oxidation to formate and then carbon dioxide. Methanol represses the growth of B. methanolicus MGA3 at levels higher than 20 mM and its metabolite formaldehyde completely halts the growth of B. methanolicus MGA3 at 1 mM external medium concentration. B. methanolicus MGA3 possess three putative formaldehyde dehydrogenases and two putative formate dehydrogenases in addition to one plasmid and two chromosomal mdh genes. qPCR results show that when challenged with 100 mM methanol, 1 mM formaldehyde or 1 mMformate, these genes are all down regulated in both mannitol-grown and methanol-grown B. methanolicus MGA3. Only pfk is upregulated in response to methanol challenge. As a candidate industrial microorganism, understanding of the cellular stress-response to methanol metabolism is crucial in order to optimize growth and the carbon flux into the assimilatory RuMP pathway.