Targeted drug delivery aims to increase the therapeutic index by making more drug molecules available at the diseased sites while reducing systemic drug exposure. In this update, we provide an overview of polymer-drug conjugates that have advanced into clinical trials. These systems use synthetic water-soluble polymers as the drug carriers. The preclinical pharmacology and recent data in clinical trials with poly(l-glutamic acid)-paclitaxel (PG-TXL) are discussed. This is followed by a summary of a variety of polymeric conjugates with chemotherapeutic agents. Results from early clinical trials of these polymer-drug conjugates have demonstrated several advantages over the corresponding parent drugs, including fewer side effects, enhanced therapeutic efficacy, ease of drug administration, and improved patient compliance. Collectively, these data warrant further clinical development of polymer-drug conjugates as a new class of anticancer agents.