Schematic overview of the major pathways involved in RCT from peripheral tissue and macrophages/foam cells. apoA-I is secreted by liver and intestine and loaded with cholesterol (CH) and phospholipids (PL) by ABCA1. The thus formed pre-β-HDL picks up cholesterol and phospholipid from ABCA1 in macrophages and peripheral cells and is converted to HDL₂. HDL₂ can be further loaded with cholesterol by ABCG1, and possibly SR-BI, in macrophages and delivers in turn its cargo to SR-BI in the liver. Zhang et al. (12), via development of a surrogate method to monitor foam cell cholesterol efflux in mice, have now shown that hepatic SR-BI is a positive regulator of macrophage RCT in vivo. Subsequently, cholesterol can be secreted into the bile either in the free form or after conversion as bile salt (BS). After transport via the bile into the intestine, cholesterol and bile salts are reabsorbed or excreted in the feces.