The unprecedented outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically changed the global approach to public health, emphasizing the importance of measures to control and prevent infections. In response to the COVID-19 crisis, stringent hygiene practices and surface disinfection have become the norm, with an unprecedented surge in the use of disinfectants and antiseptics (DAs). While these measures have been crucial in curbing the spread of the virus, an emerging concern has taken center stage: the potential impact of the prolonged and widespread use of antimicrobial compounds in these products on the development of antibiotic resistance. Antimicrobial resistance (AMR) has long been recognized as one of the most pressing global health threats. Quaternary ammonium compounds (QAC) such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium chloride, which are extensively used in DAs formulations, have gained less attention in the context of AMR. A high abundance of QACs was detected in wastewater, and certain bacteria such as , and species developed resistance to these compounds over time. We analyzed the available evidence from the scientific literature, examining the presence and concentrations of QACs in different water sources, and their resistance mechanisms. This review aimed to shed light on the multifaceted challenges that arise from the dual battle against the COVID-19 pandemic and the ongoing global fight against AMR.