The Chinese tree Camptotheca acuminata, or Xi Shu, brings us a unique class of chemotherapeutic agents known as the camptothecins. Because the parent compound exhibited excessive toxicity and poor aqueous solubility, synthetic and semisynthetic analogs were developed. These compounds contain a lactone ring that is necessary for activity and is easily hydrolyzed into the less active hydroxy carboxylic acid. Irinotecan, a semisynthetic analog is a prodrug that is cleaved by a carboxylesterase-converting enzyme to form the biologically active metabolite SN-38. The half-lives of irinotecan and SN-38 are relatively long, and both are commonly found in the lactone form. Topotecan differs from irinotecan in that it is found predominately in the inactive carboxylate form at neutral pH, but can be maintained in the lactone form at a lower pH. In phase I clinical trials, the antitumor activity of topotecan has been impressive. In vitro and in vivo studies have shown that combinations between topotecan and 5-fluorouracil or cisplatin have synergistic antitumor effects compared with topotecan alone. Two relatively new agents, 9-aminocamptothecin and GG211, have produced promising results against a variety of tumors.