Platinum-based therapy remains the standard of care for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). When combined with a third-generation agent, platinum-based doublets improve survival compared with the third-generation agent given alone. Controversy remains, however, regarding the relative risks and benefits of the third-generation agents. Four large phase III trials have addressed this question, with only one trial finding a survival benefit in one of the treatment arms. TAX 326 compared docetaxel-based therapy with vinorelbine/cisplatin, and found that survival, response, and quality of life outcomes all favoured the docetaxel/cisplatin regimen. Consistent benefits have been reported with this regimen in other studies. The non-platinum-based docetaxel/gemcitabine combination is an alternative for patients who are not suitable candidates for platinum-based therapy. Other results have shown that single-agent docetaxel is an appropriate option for elderly patients and those with poor performance status. Overall, the wealth of data with docetaxel in advanced NSCLC suggests that it plays an important role in first-line treatment and, as a single agent, can be considered a reasonable approach in elderly and frail patients.