Various forms of arsenic were used in China and elsewhere for over 5,000 years. Following the initial success of intravenous arsenic trioxide (i.v. As₂O₃), we revived an oral formulation of pure As₂O₃ in 1998 for the treatment of acute promyelocytic leukemia (APL). We were the first to produce a 1 mg/ml oral-As₂O₃ solution and showed that it had comparable bioavailability to i.v. As₂O₃. Moreover, we also reported that intracellular arsenic concentrations were considerably higher than the corresponding plasma values. Our oral-As₂O₃ was patented internationally and registered in Hong Kong for the treatment of APL. Safety, tolerability and clinical efficacy was confirmed in long-term follow-up studies. We have extended the use of oral-As₂O₃ to frontline induction of newly diagnosed APL. With these findings, we are moving toward an era of completely oral and chemotherapy-free management of APL.