► Small amounts of sulfa-drugs (SNs) are widely detected in the environment. ► SNs are still widely used in animal husbandry. ► The highest concentrations of SNs occur in manure. ► Environmental risk of SNs toxicity is insignificant. ► SNs can participate in the generation of drug resistance. World production and consumption of pharmaceuticals has been steadily increasing. Anti-infectives have been particularly important in modern therapy of microbial infection. Sulfonamides have been widely used for a long time as anti-infectives and are still widely prescribed today. This review presents the most common types of sulfonamides used in healthcare and veterinary medicine and discusses the problems connected with their presence in the biosphere. Based on the analysis of over 160 papers, it was found that small amounts of sulfonamides present in the environment were mainly derived from agricultural activities. These drugs have caused changes in the population of microbes that could be potentially hazardous to human health. This human health hazard could have a global range, and administrative activities have been ineffective in risk reduction.