Aquaculture is a rapidly growing industry that currently accounts for almost half of the fish used for human consumption worldwide. Intensive and semi-intensive practices are used to produce large stocks of fish, but frequent disease outbreaks occur, and the use of antimicrobials has become a customary practice to control them. The selective pressure exerted by these drugs, which are usually present at sub-therapeutic levels for prolonged periods in the water and the sediments, provides ideal conditions for the emergence and selection of resistant bacterial strains and stimulates horizontal gene transfer. It is now widely recognized that the passage of antimicrobial resistance genes and resistant bacteria from aquatic to terrestrial animal husbandry and to the human environment and vice versa can have detrimental effects on both human and animal health and on aquatic ecosystems. A global effort must be made to cease antimicrobial overuse in aquaculture and encourage stakeholders to adopt other disease prevention measures. Shaping a new path is crucial to contain the increasing threat of antimicrobial resistance.