Each year, a variety of novel nanomaterials are being developed with the objective of treating different diseases. However, since nanomaterials are foreign to the human body, one of the principal factors that limit their use is the encounter with the first line of defense from the body: the immune system. If this interaction is not taken into account, an undesired recognition takes place and the efficiency of nanoparticle based therapies is dramatically reduced. As such, understanding the rules that govern this recognition is of prime importance in the field of nanomedicine. Following this line of thoughts (the driving force), the work described in this dissertation takes a systematic approach to understand and use the relationship between immunological responses and the chemical nature of the nanoparticle surface. We first explored the chemical rules of the immunological recognition, to then re-engineer our materials based on the acquired knowledge, setting a final goal in the development of new nanomaterials capable of modulating immune responses. Our findings demonstrated not only the vast potential of nanomaterials for their use in immunotherapies, but also the power of Chemistry in the development of these systems.