- Publisher Summary This chapter focuses on site-specific targeting of liposome-artificial vesicles composed of one or more concentric lipid bilayers that enclose an aqueous space. Because liposomes are composed mainly of phospholipids and cholesterol, they are generally nontoxic, nonimmunogenic, and biodegradable. The principal benefits of liposomes include the possibility of delivering highly concentrated drugs entrapped in the lipid bilayer, or in the internal aqueous phase, and their protection against enzymatic degradation. The diversity of phospholipids allows endless manipulation of their biochemical and biophysical properties that facilitates the design of liposomes with specialized characteristics. Some success has been gained using targeted liposomes in vivo, yet this success was very limited because of physiological constraints that affect liposome disposition in vivo, such as the affinity of liposomes to phagocytic cells and the limited ability of liposomes to escape into the extravascular space. This chapter presents an updated report on the current knowledge and understanding of the physical constraints that confront liposomes on their route from the administration site to the target cells and provides some practical approaches to overcome these obstacles.