The ability to mediate targeted and specific delivery of therapeutics to cancer cells remains one of the most important hurdles in effectively treating cancer. This aspect also remains as one of the greatest limitations of gene therapy as well. Targeted vectors based on the use of DNA-binding agents attached to cell specific ligands or “molecular conjugates” were created with the goal of over-coming this hurdle. Since being conceived, many different ligands have been utilized as molecular conjugates, targeting the resulting Protein/DNA polyplex to cells efficiently in vitro while mediating limited delivery in vivo. This limited delivery is due to many reasons such as the need to identify non-viral agents that can aide in escaping endosome entrapment as well as decreasing the complexity that has evolved in the creation of these “synthetic viruses”. This review will discuss the current status and the future of molecular conjugates as targeting vectors as well as the positive and negative attributes of this vector in relation to other viral and non-viral vectors that are currently used in many gene therapy strategies.