Carotenoids are plant pigment molecules that are potent antioxidants. Carotenoids cannot be synthesized de novo; therefore, their dietary intake and transport to various tissues are essential to harness their health benefits. Two of the three scavenger receptor class B (SRB) proteins, SR-B1 and CD36, have been implicated as carotenoid transporters in lower species and in various tissues of higher animals. The function of the third SRB protein, SR-B2, in carotenoid transport is unknown. Using surface plasmon resonance (SPR) analyses, we have determined that all three human SRB proteins are capable of binding the macular xanthophyll carotenoids; lutein, zeaxanthin, and meso-zeaxanthin. By over-expressing human SRB proteins in cells that do not endogenously express SRBs, we have determined that lutein uptake is enhanced in the presence of LDL and is mediated by SR-B1 and CD36. SR-B1, SR-B2, and CD36 were able to take up significant amounts of zeaxanthin as well as meso-zeaxanthin, and uptake was increased in the presence of HDL. Our analyses revealed no apparent differences in protein expression profiles of SRBs in central and peripheral regions of human donor tissues, indicating that carotenoid-binding proteins rather than transporters are likely to mediate selective accumulation of carotenoids into the macula.