Etoposide remains an integral component of therapy for non-small cell lung cancer. Its single-agent activity, and, hence, its activity in combination therapy, need to be reassessed in light of several reports of increased activity at higher doses. Although no effective means of overcoming resistance to etoposide appear to exist, topoisomerase II levels may predict sensitivity to treatment. Biologic response modifiers appear to add little or nothing to standard etoposide chemotherapy for non-small cell lung cancer. Continuous low-dose etoposide infusions do not appear to exhibit the same degree of activity as has been observed with prolonged oral dosing. The availability of effective means of reducing hematologic and emetic side effects of chemotherapy may permit rational trials of more intensive therapy.