The paper essentially summarizes and provides a comprehensive evaluation of degeneration of substrate utilization in terms of short and long term effects and biodegradability of the selected antibiotics; sulfamethoxazole, erythromycin, and tetracycline; under different conditions. This review focuses on acute and chronic tests to evaluate the inhibitory effects of the antibiotics and to control them at the source. Acute impact based on batch tests was conducted using antibiotic dozing in the range of 1-1000 mg/L. Substrate removal was monitored by means of soluble COD and VFA measurements. At low antibiotic dosing VFA mixture was completely removed; at higher doses propionate utilization was impaired and butyrate was reduced. Higher doses induced total inactivation of microbial metabolism. For chronic impacts, the antibiotic dozing was gradually increased in lab-scale anaerobic reactors. COD, VFA, and methane generation were monitored during each phase. For each antibiotic, a threshold concentration level was determined, which did not impair substrate utilization. High concentration of antibiotics (3 mg/L<) caused toxic effects on the mixed microbial culture and affected substrate removal and biogas generation and finalized a total collapse of the reactors. Each antibiotic reflected a different impact and biodegradation pattern related to its specific mode of action. Complete removal of antibiotics could be achieved at low concentration levels. The main removal mechanism for all three antibiotics was biodegradation and not sorption. When the sorption increased in the system, the system collapsed.