The potential health effects associated with the widespread use of engineered nanomaterials are broadly concerning to developers, researchers, and policy-makers alike. While extensive studies have been undertaken to understand the immediate consequences of exposure to these materials, the long-term effects associated with potential translocation to secondary and even tertiary organs are less well understood. Further, mechanisms underlying the toxic properties of nanomaterials after translocating to distal organs, if any, are largely unknown at this time. Here, we describe the current state of knowledge regarding translocation of commonly studied and primarily nonmedical engineered nanomaterials following exposure and discuss potential mechanisms and consequences to health outcomes. Current evidence suggests that nanomaterials are redistributed, at least in part, to secondary organs throughout the body. While the properties associated with any given nanomaterial may influence its redistribution, the most likely explanation for adverse effects following translocation involves increased inflammation leading to pathology. Whether more persistent nanomaterials will eventually be cleared from the body after exposure remains an important question. Further, information regarding the effects of systemic trafficking on the basic characteristics of nanomaterials would help predict whether nanomaterials will accumulate in specific organs and/or cause pathologies in secondary or even tertiary locations.