Arsenic trioxide (As(2)O(3)) for leukaemia treatment was described a century ago. Recent resurgence in the use of arsenic trioxide is related to its high efficacy in acute promyelocytic leukaemia (APL). Most arsenic trioxide preparations are intravenous, although an oral formulation is similarly efficacious. Side effects of arsenic trioxide are usually minor, including skin reactions, gastrointestinal upset, and reversible increases in transaminases. During therapy, a leukocytosis occasionally occurs, which may be complicated by fluid accumulation and pulmonary infiltration. Arsenic trioxide causes an asymptomatic QT prolongation in most patients. However, if concomitant cardiopulmonary diseases or electrolyte disturbances are present, more sinister arrhythmias may develop. Therefore, before commencement of arsenic trioxide therapy, a full cardiac assessment and avoidance of drugs that prolong QT interval should be instituted. Arsenic trioxide is partly renally excreted and, therefore, dose adjustment is required when renal function is impaired. In addition to its use in APL, arsenic trioxide is now tested in other malignancies, notably multiple myeloma.