Performance status (PS)2 patients with advanced non-small-cell lung cancer have been historically excluded from clinical trials, and scant data are available to guide clinical practice. As in other types of cancer, PS represents a recognized prognostic factor, and the life expectancy for PS2 patients is nearly half that of the PS0/1 patients. Even if single-agent chemotherapy still remains the reference treatment, recent data suggest a role for new agents or combination chemotherapy in these patients. A large Phase III randomized trial comparing single-agent versus combination chemotherapy is strongly needed.