Adenoviruses (Ads) are the most frequently used viral vectors in gene therapy and cancer therapy. Obstacles to successful clinical application include accumulation of vector and transduction in liver cells, coupled with poor transduction of target cells and tissues such as tumours. Many host molecules, including coagulation factor X, have been identified and suggested to serve as mediators of Ad liver tropism. This review summarises current knowledge concerning these molecules and the mechanisms used by Ads to bind to target cells, and considers the prospects of designing vectors that have been detargeted from the liver and retargeted to cells and tissues of interest in the context of gene therapy and cancer therapy.