Targeting drug delivery system (TDDS) is one of the most concerned research fields in cancer treatment because it can bind selectively and react with the target diseased sites at the cellular or sub-cellular level, making distribution and release of drugs in a controlled manner, thus enhance therapeutic effects and reduce toxic and side-effects on normal cells. Polyamidoamine dendrimer (PAMAMD) is a kind of newly developed polymer in nanometer degree. Hyper-branched, monodispersity, three-dimensional structure and host-guest entrapment ability make it used as drug carrier, gene delivery system and imaging agent. Various targeting ligands, which have high affinity to specific organs, tissues or cells in human body, can be linked to surface functional groups of PAMAMD. And drugs and theoretical gene are carried by encapsulation or chemical conjugation. Finally, PAMAMD targeting drug delivery system can carry drugs and theoretical gene to diseased sites and then release them for targeted therapy. The PAMAMD-based conjugates have small size, ligh permeability and retention effect (EPR), low toxicity and so on. The research progress of PAMAMD modified by different ligands in targeting drug delivery system is reviewed, and research direction of the PAMAMD targeting delivery system in the future is also suggested.