Inflammation is a primordial response that organisms set up to counteract the invasion of pathogens and attack by any other xenobiotic; the symptoms characteristic of inflammation are well known, the classic rubor, dolor, calor, tumor and functio laesa being described since ancient times. This response of the host is complex and multifactorial, and crucial for survival: abnormal inflammation, as in the case of patients affected by leukocyte adhesion deficiency, a genetic disease whereby specific adhesion molecules are absent, is associated with poor life quality and precocious death. Fighting inflammation is a common problem that physicians have to face when dealing with a wide variety of diseases. Hence, understanding the molecular and cellular mechanism responsible for it is important for the design of a better therapy. Modern theories in this field of research have suggested that one way to achieve a better and more efficient antiinflammatory therapy is to exploit the bodys own arsenal of endogenous antinflammatory mediators. One such protein is Annexin-1 (AnxA1): an endogenous anti-inflammatory protein whose activity correlates to the pharmacological effects of glucocorticoids. In this review we will summarize the most recent studies on the biological effects of AnxA1 and in particular we will be focusing on the differential and yet complementary role of this protein in the innate and adaptive immune systems.