The paper mainly focused on illustrating the merit of respirometric analysis in assessing the inhibitory/toxic impact of xenobiotics on substrate biodegradation. It also evaluated biodegradation characteristics of these chemicals at continuous exposure through acclimation ofthe microbial culture. The nature and role ofoxygen uptake rate (OUR) profiles were discussed in conjunction with appropriate modelling, which should incorporate dissolved oxygen as an indispensable component for respirometric evaluation. Emphasis was placed upon differentiating acute effects from chronic impact, which may be totally different as it involves biodegradation of the chemical due biomass acclimation. Three case studies, each involving OUR measurements and process modelling, were presented for this purpose. The first one related to the inhibitory action of pharmaceutical effluent when mixed with plain-settled tannery wastewater. The second investigated the fate of H-acid, a commercially important naphthalene sulfonate, which exerted no adverse effect on substrate biodegradation, while remaining intact before and after a long acclimation period. The third one involved 2,6-dihydroxybenzoic acid, a naturally occurring organic compound in olive oil wastewater, which became biodegradable after acclimation by the development ofa specific microbial biomass fraction, while it heavily inhibited substrate biodegradation at first exposure. Model evaluation of the experimental data could provide related information on process stoichiometry and kinetics in all studies.