The union of aquaculture and hydroponics is named aquaponics—a system where microorganisms, fish and plants coexist in a water environment. Bacteria are essential in processes which are fundamental for the functioning and equilibrium of aquaponic systems. Such processes are nitrification, extraction of various macro- and micronutrients from the feed leftovers and feces, etc. However, in aquaponics there are not only beneficial, but also potentially hazardous microorganisms of fish, human, and plant origin. It is important to establish the presence of human pathogens, their way of entering the aforementioned systems, and their control in order to assess the risk to human health when consuming plants and fish grown in aquaponics. Literature analysis shows that aquaponic bacteria and yeasts are mainly pathogenic to fish and humans but rarely to plants, while most of the molds are pathogenic to humans, plants, and fish. Since the various human pathogenic bacteria and fungi found in aquaponics enter the water when proper hygiene practices are not applied and followed, if these requirements are met, aquaponic systems are a good choice for growing healthy fish and plants safe for human consumption. However, many of the aquaponic pathogens are listed in the WHO list of drug-resistant bacteria for which new antibiotics are urgently needed, making disease control by antibiotics a real challenge. Because pathogen control by conventional physical methods, chemical methods, and antibiotic treatment is potentially harmful to humans, fish, plants, and beneficial microorganisms, a biological control with antagonistic microorganisms, phytotherapy, bacteriophage therapy, and nanomedicine are potential alternatives to these methods.