Liver diseases, particularly hepatitis B virus infections, liver cirrhosis and hepatocellular carcinoma continue to pose a significant health challenge worldwide due to the dire lack of curative treatment options besides liver resection and transplantation. Nanoparticle therapeutics, comprising of drugs, nucleic acids or proteins in association with a carrier, have emerged as safe and efficient systems in the treatment of the respective liver diseases. This review describes targeting strategies employed in relation to liver anatomy and disease etiologies, summarizes recent advances in the field and discusses the challenges and future perspectives for the effective treatment of liver diseases using polymer- and lipid-based nanoparticle therapeutics. (C) 2010 Elsevier Ltd. All rights reserved.