—Cancer represents the most life threatening disease worldwide where cells lose their normal regulatory mechanism that control their growth hence cells grow out of control resulting in a mass known as tumor. It shows complicated protocols of treatment, as the major limitation of most conventional anticancer therapy is the lack of tumor selectivity and killing of both normal and abnormal cells. Recently, several interests were introduced in the field of Drug Delivery Systems (DDS) in order to enhance the therapeutic effect and decrease the side effects of anticancer drugs. Several mechanisms have been introduced to moderate the effect of DDS, among them passive drug targeting, where the drug is incorporated into surface modified nanocarriers such as liposomes, niosomes, solid lipid Nanoparticles (NP) and Nanoemulsions (NE). Surface modification is achieved by increasing the hydrophilicity of the DDS since, it is known that hydrophobic surfaces tends to absorb high amount of proteins. Among hydrophilic polymer, PEG, PVA, dextran. However, PEG is the most frequently hydrophilic polymer applied for surface modification that increase the circulation time of nanocarriers and reduce the liver uptake compared to nonsurface modified one. The Enhanced Permeability and Retention (EPR) effect is a phenomenon of tumor cells related to their anatomical and pathophysiological structure and their variations from normal tissues. EPR effect provides long-circulating PEG nanocarriers with a high opportunity to target tumor cells following systemic administration. In the current review a brief summary regarding nanocarriers and its mechanism as a drug targeting systems are discussed.