Poly(amidoamine) (PAMAM) dendrimers are a novel class of spherical, well-designed branching polymers with interior cavities and abundant terminal groups on the surface which can form stable complexes with drugs, plasmid DNA, oligonucleotides, and antibodies. AmineaEuroterminated PAMAM dendrimers are able to solubilize different families of hydrophobic drugs, but the cationic charges on dendrimer surface may disturb the cell membrane. Therefore, surface modification by PEGylation, acetylation, glycosylation, and amino acid functionalization is a convenient strategy to neutralize the peripheral amine groups and improve dendrimer biocompatibility. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumor via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Biodegradability, non-toxicity, non-immunogenicity, and multifunctionality of PAMAM dendrimer are the key factors which facilitate steady increase of its application in drug delivery, gene transfection, tumor therapy, and diagnostics applications with precision and selectivity. This review deals with the major topics of PAMAM dendrimers including structure, synthesis, toxicity, surface modification, and also possible new applications of these spherical polymers in biomedical fields as dendrimer-based nanomedicine.