In the late 1980s, we and colleagues described unique cases of treatment-related acute myeloid leukaemia (AML) in patients who had received intensive chemotherapy, including the epipodophyllotoxins, for acute lymphoblastic leukaemia (ALL) or solid tumours (Ratain et al, 1987; DeVore et al, 1989; Pui et al, 1989, 1990; Albain et al, 1990; Pedersen-Bjergaard et al, 1990; Prieto et al, 1990). A causative role of the epipodophyllotoxins was suspected but could not be established unequivocally. Thus, the terms secondary AML and therapy-related AML were used to describe these cases. By 1991, the leukaemogenic potential of the epipodophyllotoxins was firmly established (Pui et al, 1991), leading to the term epipodophyllotoxin-related AML (Pui, 1991; Whitlock et al, 1991). It has since been recognized that other topoisomerase II inhibitors, such as the anthracyclines (doxorubicin, 4-epi-doxorubicin), mitoxantrone, dactinomycin and dioxypiperazine derivatives (eg bimolane), can also induce AML with similar features, albeit at a lower frequency (Andersson et al, 1990; Pui, 1991; Pedersen-Bjergaard et al, 1992; Xue et al, 1992; Sandoval et al, 1993; Pedersen-Bjergaard & Rowley, 1994; Smith et al, 1996). Collectively, these cases have been classified as topoisomerase II inhibitor-related leukaemia (Ratain & Rowley, 1992; Pedersen-Bjergaard et al, 1993; Sandoval et al, 1993; Smith et al, 1995). We review here the pathogenesis, clinical and biological characteristics, risk factors and treatment responsiveness of this complication.