Considerable evidence points to the immune system as a formidable barrier to the proper function of nanomaterials in the body. Results from both experimental models and clinical applications suggest that one of the major current challenges in nanomedicine is to permit unhindered circulation of vehicles for drug delivery or tissue repair. Biocompatibility of these vehicles has been sought out by using materials with a biological origin that ensure low toxicity and biodegradability. However, as discussed in this chapter, the resemblance between physicochemical properties of such materials and products from microbial organisms prompts a diversified response from the immune system.