In more than 30 years of research annexins have been demonstrated to regulate immune responses. The prototype member of this family, annexin (Anx) A1, has been widely recognized as an anti-inflammatory mediator affecting migration and cellular responses of various cell types of the innate immune system. Evidently, effects on innate immune cells also impact on the course of adaptive immune responses. Innate immune cells provide a distinct cytokine milieu during initiation of adaptive immunity which regulates the development of T cell responses. Moreover, innate immune cells such as monocytes can differentiate into dendritic cells and take an active part in T cell stimulation. Accumulating evidence shows a direct role for annexins in adaptive immunity. Anx A1, the annexin protein studied in most detail, has been shown to influence antigen presentation as well as T cells directly. Moreover, immune modulatory roles have been described for several other annexins such as Anx A2, Anx A4, Anx A5 and Anx A13. This review will focus on the involvement of Anx A1 and other annexins in central aspects of adaptive immunity, such as recruitment and activation of antigen presenting cells, T cell differentiation and the anti-inflammatory removal of apoptotic cells.