The amount of nanoparticles (NPs) in human environment is increasing. The main sources are the increased introduction in consumer products and air pollution (diesel exhaust). It is meanwhile common knowledge that NPs behave differently as bulk material because of their nano-size. This leads in general to a higher reactivity and some other changed properties, e.g. solubility, surface potential, conductivity, and, to different effects on biological systems. The main impacts of NPs on a cellular and organism level are meanwhile well known: release of toxic ions, increased oxidative stress, and inflammation. Beside these, there is increasing evidence that NPs, especially in low dose/long exposure scenarios, affect biological systems in a broader way, interact with drugs, and exacerbate the effects of diseases. To investigate these effects systems biology approaches are the method of choice. This review summarizes the state of the art of nanoparticle effects on cells and organisms and demonstrate the add value of systems biology investigations to NP hazard assessment.