Here we report a new and efficient approach of macrophage specific drug delivery by coating liposomes with albumin. Activated albumin was reacted with liposomes containing polyethylene glycol (PEG) as hydrophilic spacers to create a flexible layer of covalently bound albumin molecules on the liposome surface. Albumin coated liposomes were taken up faster and more efficiently than uncoated liposomes by murine macrophages. Liposome uptake was significantly higher in macrophages as compared to other cell types tested (endothelial cells, fibroblasts, tumor cells), suggesting specificity for macrophages. In vivo, splenic macrophages phagocytosed BSA coated liposomes (BSA-L) at faster rates compared to conventional liposomes (L) and PEG liposomes (PEG-L). To prove the effectiveness of this new macrophage specific drug carrier, the bisphosphonates clodronate and zoledronate were encapsulated in BSA-L and compared with conventional liposomes. In vitro, treatment of macrophages with clodronate or zoledronate in BSA-L led to cytotoxic activity within a very short time and to up to 50-fold reduced IC50 concentrations. In vivo, clodronate encapsulated in BSA-L depleted splenic macrophages at a 5-fold lower concentration as conventional clodronate-liposomes. Our results highlight the pharmaceutical benefits of albumin-coated liposomes for macrophage specific drug delivery.