The discovery of new diverse and novel applications for engineered nanomaterials (ENMs) creates possibilities of inadvertent release in the environment. The interactions of ENMs with living systems and possible impact/adverse effects cannot be predicted due to novel size and physiochemical properties. The biological variability, dose dilemma, exposure methods, lack of suitable models and reference materials are certain important constraints in risk assessment of ENPs. Hence, we have explored the efficacy of microorganisms as models to understand uptake, accumulation and mechanism of adverse effects induced by selected nanoparticles.