Macrophages are key players of the immune system and express a variety of surface receptors. CD163 is one such receptor which belongs to the scavenger receptor cysteine-rich super family (SRCR-SF) class B. It has four isoforms which differ in the structure of their cytoplasmic domains and putative phosphorylation sites. Expression of CD163 is tightly regulated with a general tendency of anti-inflammatory signals to induce its synthesis, while pro-inflammatory signals downregulate its expression. Previously the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes. However, it also plays a crucial role in the control of inflammatory processes by induction of anti-inflammatory pathways. Soluble CD163, which is generated via ectodomain shedding, serves as a potential diagnostic tool in a variety of disease states, such as inflammation, atherosclerosis, transplant rejection and carcinoma. Recently, CD163 has been identified as a promising target for cell directed therapy. In this review we aim to summarize the current knowledge of CD163.