Despite the very good response rate of small cell lung cancer (SCLC) to many anti-cancer agents, survival remains disappointing, particularly in extensive-stage (ES) disease. Many potentially beneficial regimens have achieved a median survival of less than 12 months in clinical trials, and so the standard regimen has remained cisplatin plus etoposide. Trials have shown that 3- and 4-drug regimens are no better than 2-drug regimens; alternating agents, dose-dense and high-dose regimens do not improve outcome, and non-platinum-based regimens are not superior to platinum-based regimens. A recent phase II trial demonstrated that pemetrexed/platinum-based doublets are active in ES-SCLC in the first-line setting. In combination with cisplatin or carboplatin, pemetrexed demonstrated a favourable toxicity profile. The ease of administration and convenient schedule of pemetrexed make these regimens attractive. Although further follow-up of patients in this trial is necessary to define response durability and survival, results so far have led to the initiation of phase III trials of pemetrexed-based regimens in ES-SCLC.