Drug delivery to liver is one of the most challenging research areas in pharmaceutical sciences. The some physiological barrier such as opsonization, mechanical entrapment by pulmonary vascular bed, uptake by RES represents an insurmountable obstacle for a large number of proteins and drugs, including antibiotics, antineoplastic agents and antiviral agents to target liver disorders. Therefore, various strategies have been proposed to improve the delivery of different drugs to liver and hepatocytes which includes passive accumulation of nanoparticle therapeutics and active targeting by surface modifications of nanoparticles with specific ligands such as carbohydrates, peptides, proteins and antibodies. The present review enlightens about different pathologies of liver and targeting strategies employed in relation to liver anatomy and disease etiologies.