Anaerobic digestion has been frequently used to treat antibiotic-contaminated livestock wastewaters. In these systems, the removal of antibiotics is mainly related to biodegradation and adsorption to the sludge. In this sense, a better understanding of the mechanisms involved in the removal of the veterinary antibiotic sulfamethazine in a horizontal-flow immobilized biomass reactor could be achieved by the mathematical evaluation of the physical and biochemical phenomena occurring in the reactor. It was found that two distinct models were capable of accurate representation of the experimental observations of total chemical oxygen demand, total acids produced/consumed, biomass and sulfamethazine. In addition, the sulfamethazine degradation was mainly related to acids consumption.