Human’s quest for innovation, finding solutions of problems, and upgrading the industrial yield with energy efficient and cost-effective materials has opened the avenues of nanotechnology. Among a variety of nanoparticles, zinc oxide nanoparticles (ZnO) have advantages because of the extraordinary physical and chemical properties. It is one of the cheap materials in cosmetic industry, nanofertilizers, and electrical devices and also a suitable agent for bioimaging and targeted drug and gene delivery and an excellent sensor for detecting ecological pollutants and environmental remediation. Despite inherent toxicity of nanoparticles, synthetic routes are making use of large amount of chemical and stringent reactions conditions that are contributing as environmental contaminants in the form of high energy consumption, heat generation, water consumption, and chemical waste. Further, it is also adding to the innate toxicity of nanoparticles (NPs) that is either entirely ignored or poorly investigated. The current review illustrates a comparison between pollutants and hazards spawned from chemical, physical, and biological methods used for the synthesis of ZnO. Further, the emphasis is on devising eco-friendly techniques for the synthesis of ZnO especially biological methods which are comparatively less hazardous and need to be optimized by controlling the reaction conditions in order to get desired yield and characteristics.