Oxaliplatin (Eloxatin) is a novel antineoplastic platinum derivative that may exert its cytotoxic effects by blocking DNA replication/transcription, thus resulting in cell death in proliferating cells, as well as apoptosis. Oxaliplatin is often more potent than other platinums such as cisplatin (Platinol) in vitro, and shows greater efficacy in preclinical studies against many tumor cell lines, including some that are resistant to cisplatin and carboplatin (Paraplatin). Oxaliplatin is approved for use with the fluoropyrimidines in the treatment of metastatic colorectal cancer in Asia, Latin America, and Europe. In light of the broad efficacy of oxaliplatin in several solid tumors and the encouraging preclinical data on combination therapy with novel agents (e.g., thymidylate synthase inhibitors, epidermal growth factor-receptor antagonists, microtubule interactive agents), this article will review the published literature on novel combinations that have been tested in the laboratory and/or the clinic.