The introduction of targeted biological agents represents the most promising approach to improve the disease control and outcome for patients with non-small cell lung cancer. The epidermal growth factor and the vascular endothelial growth factor signaling pathways have been successfully targeted using both orally administered small molecule tyrosine kinase inhibitors and monoclonal antibodies, with associated improvement in overall survival. Although the trials that established the efficacy of these agents allowed the enrollment of patients older than 70 years, the elderly patients constituted the minority. Given the stringent enrolment criteria in terms of organ function and performance status for most clinical trials, the elderly patients on clinical trials are not entirely representative of the overall elderly patient population. Therefore, the applicability of these data to the overall patient population deserves critical appraisal in the absence of trials dedicated specifically to the elderly. Preplanned and unplanned subset analysis of registration trial data is becoming increasingly common as a substitute measure to provide valuable information to guide the use of targeted agents in the elderly. Using this approach, it has been demonstrated that elderly patients are able to tolerate targeted biological therapies but suffer increased rate of toxicities. However, they derive benefit from such agents when they are carefully selected and have their drug doses adjusted appropriately to minimize potential toxicities. This article reviews the use of targeted agents for the treatment of NSCLC in elderly patients.