Treated wastewater (TWW) has become recently a valuable and significant resource for crop production in irrigated agriculture. Use of TWW for irrigation includes benefits (e.g., conservation of nutrients), yet it also poses notable risks to crop production, soil ecosystem, the environment and human health. This review discusses risks arising from using TWW that include elevation of soil water osmotic pressure, addition of toxic ions and organic contaminants to the soil, deterioration of soil physical and hydraulic properties, hazard of surface and ground water contamination by dissolved organic matter, epidemiological threats to humans and animals, and increased abundance and diversity of antibiotic resistant bacteria and genes. Current knowledge highlights the importance of recognizing and elucidating the processes by which irrigation with TWW may lead to contamination of the soil ecosystem and the necessity to develop possible management practices that could mitigate these hazards and enhance the sustainability of TWW irrigation.