During the past two decades, clinical research has focused on developing chemotherapeutic regimens that effectively prolong survival and provide palliation for patients with non-small-cell lung cancer (NSCLC). In the mid-to late-1990s, several new agents emerged from clinical development and demonstrated activity against this disease, including the novel antimetabolite gemcitabine. Gemcitabine is one of the most active agents for the treatment of NSCLC. When combined with a platinum analog, gemcitabine produces the best progression-free survival outcome of any platinum-based regimen in first-line advanced NSCLC treatment setting. On the basis of its excellent antitumor activity and favorable toxicity profile, gemcitabine has been approved for the first-line treatment of locally advanced or metastatic NSCLC.