Adaptive immunity is an active component of the host response to all medical devices used in the human body. Depending on the material, lymphocytes, the main cell type of the adaptive immune system, either actively contribute to material destruction and rejection or produce a cytokine milieu that leads to fibrosis or possibly material tolerance. Since biomaterials are increasingly used in combination products (drug delivery devices, gene delivery devices, adjuvants for vaccines, tissue engineering constructs, regenerative medicine constructs, etc.), the adaptive response to the material component can be critical to the viability and function of the entire construct. Indeed the other components of such combination products might also alter the adaptive immune response to the material; in fact, some methods of modifying the adaptive response to a biomaterial construct include adding another component to the construct, such as a drug (e.g. a corticosteroid). This article explains how the immune system recognizes biomaterials, and the consequences of the adaptive immune response to biomaterials and constructs that are known to contain biomaterials. The final section of this article provides an overview of approaches that may be used to alter the adaptive immune response to a material.