Understanding mechanisms governing the interaction of biota and nanomaterials is key to proper risk assessment and safe nanomaterial design. This applies to both the development of nanomaterials that are intended to interact with biological entities, such as for targeted drug delivery or for antibacterial activity, as well as to the identification and evaluation of unwanted effects, such as the destruction of healthy cells in human tissue or the deterioration of microbial populations in biological water treatment. Thus, knowledge of mechanisms of biota nanomaterial interaction provides a basis to derive a causally linked chain of arguments to evaluate whether a particular nanomaterial is likely hazardous or benign. This knowledge must then be placed in the context of exposure and bioavailability (Chapter 5) to assess the risk of an ensuing toxicity. Here, the term "toxic" implies a detrimental impact (or adverse outcome) that cannot be repaired and leads to effects that threaten vital functions of organisms or tissues either immediately or over a prolonged time span. Such a toxic outcome ensues when cellular barriers and stress responses are overwhelmed. Figure 6.1 illustrates the arrangement of environment organism and organism internal barriers which, if overcome, lead to true internalization and distribution of nanomaterials in the organism. Any of the cells forming barriers, or cells comprising tissues or organs, can elicit stress responses to maintain cellular homeostasis that maybe disrupted by a nanomaterial, leading to toxicity. [...]