The most common gene transfer vehicle used in gene therapy protocols are mammalian virus vectors. Specifically, retroviruses are one of the most common viral vectors used since they are able to permanently integrate their transgene into the host cell genome, providing, in principal, to a long-term cure. The potential applications of gene therapies are vast, ranging from monogenic disorders such as cystic fibrosis to complex gene disorders such as cancer. However, the application of such therapies in clinical settings has been limited partially because of inefficient gene delivery of the therapeutic gene to diseased cells. Furthermore, safety concerns of accidently altering the genetic expression in healthy bystander cells or nearby tissue has increased the interest in creating targeted viral vectors which infect only the diseased cells without infecting others. Thus, the success of gene therapy will depend on identifying and understanding the parameters critical for virus entry into cells, including factors that facilitate virus absorption onto the cell surface, virus binding, and fusion. The objective of this thesis was to understand the role of lipids in binding and infection, and to investigate the use of lipid-based conjugates to alter the surface of virus particles.