The most attractive properties of engineered nanomaterials for technological applications, including their small size, large surface area, and high reactivity, are also the main factors for their potential toxicity. Based on ambient ultrafine particle research, it is predicted that nanosized particles may have deeper pulmonary deposition, higher biological activity, and a tendency for extrapulmonary translocation compared to larger particles. In this regard, nanoparticle exposure, by direct or indirect mechanisms, may lead to unexpected distant responses, involving the immune system, cardiovascular system, liver, kidney, and brain. The systemic effects may induce or modify the progression of existing diseases such as cardiovascular disease. Current experimental toxicity evaluation of engineered nanomaterials, specifically carbon nanotubes, demonstrated that deposition of these materials in the lung leads to inflammation and fibrosis. The local toxicity is associated with cardiovascular effects related to atherosclerosis. Although translocation of carbon nanotubes into the systemic circulation is hypothetically possible, there is no current evidence to support this hypothesis. However, studies pointed out that carbon nanotube-induced lung inflammation results in a release of inflammatory mediators and activation of blood cells which can contribute to cardiovascular adverse effects. Furthermore, complex protein and gene expression blood analysis can help in development of biomarkers for application in human screening of nanoparticle exposure. Future studies to evaluate the systemic effects of carbon nanotube exposure under workplace or environmental exposure paradigms should be conducted.