Antibiotic resistance (AR) refers to bacteria’s ability to withstand the problem of resistance to which they were previously susceptible. It develops in bacteria due to genetic alterations or the acquisition of antibiotic-resistant genes (ARGs). ARGs are introduced into aquatic bodies through urban runoff, aquaculture, agriculture, animal husbandry and hospital and treatment plant effluent. Most river systems have relatively high rates of antibiotic-resistant bacteria (ARB) (98% of overall bacteria discovered), followed by lakes (77% of total bacteria discovered) and ponds and springs (less than 1%). These resistant bacteria can transmit their genes to water-borne microbes that have such resistance genes. Antibiotic-resistant microorganisms and ARGs found in water habitats can be harmful to humans if consumed. ARB infections are associated with increased mortality and morbidity rates and are expected to kill 10 million people worldwide by 2050. Thus, AR has developed a global health threat accounting for hundreds of thousands of deaths each year. This chapter highlights the current knowledge regarding the ARBs and ARGs in aquatic environments, their health risks and effective monitoring and mitigating strategies.