As demand for fresh water intensifies, wastewater is frequently being seen as a valuable resource. Furthermore, wise reuse of wastewater alleviates concerns attendant with its discharge to the environment. Globally, around 20 million ha of land are irrigated with wastewater, and this is likely to increase markedly during the next few decades as water stress intensifies. In 1995, around 2.3 billion people lived in water-stressed river basins and this could increase to 3.5 billion by 2025. We review the current status of wastewater irrigation by providing an overview of the extent of the practice throughout the world and through synthesizing the current understanding of factors influencing sustainable wastewater irrigation. A theme that emerges is that wastewater irrigation is not only more common in water-stressed regions such as the Near East, but the rationale for the practice also tends to differ between the developing and developed worlds. In developing nations, the prime drivers are livelihood dependence and food security, whereas environmental agendas appear to hold greater sway in the developed world. The following were identified as areas requiring greater understanding for the long-term sustainability of wastewater irrigation: (i) accumulation of bioavailable forms of heavy metals in soils, (ii) environmental fate of organics in wastewater-irrigated soils, (iii) influence of reuse schemes on catchment hydrology, including transport of salt loads, (iv) risk models for helminth infections (pertinent to developing nations), (v) microbiological contamination risks for aquifers and surface waters, (vi) transfer efficiencies of chemical contaminants from soil to plants, (vii) health effects of chronic exposure to chemical contaminants, and (viii) strategies for engaging the public.