The development of the organisms extracellular and intracellular mechanisms for the uptake of heavy metals were conducted by using the natural detoxification strategies of the organism to toxicity. Aspergillus foetidus was used as a test case organism to examine these processes. Aspergillus foetidus was adapted to multi-metals (Al, Co, Cr, Cu, Fe, Mg, Mn, Ni and Zn) by a sequential method for tolerance development. The detoxification strategies of A. foetidus occurred by two mechanisms. The first mechanism is the production of extracellular metabolites that is capable of adsorbing and precipitating the metal ions on the cell surface. The second mechanism for the detoxification of metals is the intracellular binding of heavy metals to thiol containing compounds such as GSH and sequestering these metal–thiol complexes into sub-cellular compartments or vacuoles. These detoxification strategies resulted in adapted organisms with tolerance to multi-heavy metals concentrations and significantly higher metal uptake with adaptation.