The prognosis is poor for patients relapsing following treatment with standard chemotherapy for aggressive non-Hodgkin's lymphoma. High-dose therapy and autologous stem cell transplantation is a potential curative approach for these patients. The primary aim of second-line therapy is the attainment of a complete response, because response rate is predictive of outcome following autologous stem cell transplantation. A number of strategies have been explored to improve the complete response rate to standard second-line regimens. Ifosfamide, carboplatin, and etoposide (ICE) can offer an improved response rate compared with the standard regimens of dexamethasone, cisplatin, and cytarabine (DHAP) and etoposide, methylprednisolone, high-dose cytarabine, and cisplatin (ESHAP). The addition of rituximab to ICE improves the complete response rate compared with ICE alone. Because the addition of rituximab to chemotherapy regimens leads to improved complete response rates compared with chemotherapy alone, it should be considered as an important component of second-line regimens for aggressive NHL.