The advantages and disadvantages of macromolecular drugs, particularly on synthetic polymer-protein conjugates, are described in this article. Improvements in protein drugs, after tailoring with polymers, are as follows: increased plasma half-life, loss of antigenecity, lymphotropism, and, especially, preferred tumor-targeting efficiency and long-term retention in the tumor tissues. Hydrophobic character can make a drug also possible for oily formulation. Explained are the rationales of macromolecular drugs to preferential delivery to the tumor and lymphatic tissues based on our finding on pathological/anatomical differences of the blood and lymphatic vasculatures. Enhanced vascular permeability, which facilitates the macromolecular drug-leakage out of the blood vessel, is discussed. A model compound, which is discussed in detail, is smancs--styrene-co-maleic acid conjugated neocarzinostatin (MW 16 K). Some data on polymer-conjugated enzymes as potential therapeutic agents are described as well.