The most adverse outcome of increasing industrialization is contamination of the ecosystem with heavy metals. Toxic heavy metals possess a deleterious effect on all forms of biota; however, they affect the microbial system directly. These heavy metals form complexes with the microbial system by forming covalent and ionic bonds and affecting them at the cellular level and biochemical and molecular levels, ultimately leading to mutation affecting the microbial population. Microbes, in turn, have developed efficient resistance mechanisms to cope with metal toxicity. This review focuses on the vital tolerance mechanisms employed by the fungus to resist the toxicity caused by heavy metals. The tolerance mechanisms have been basically categorized into biosorption, bioaccumulation, biotransformation, and efflux of metal ions. The mechanisms of tolerance to some toxic metals as copper, arsenic, zinc, cadmium, and nickel have been discussed. The article summarizes and provides a detailed illustration of the tolerance means with specific examples in each case. Exposure of metals to fungal cells leads to a response that may lead to the formation of metal nanoparticles to overcome the toxicity by immobilization in less toxic forms. Therefore, fungal-mediated green synthesis of metal nanoparticles, their mechanism of synthesis, and applications have also been discussed. An understanding of how fungus resists metal toxicity can provide insights into the development of adaption techniques and methodologies for detoxification and removal of metals from the environment
