Non-small-cell lung cancer (NSCLC) is a leading cause of malignancy-related mortality in the Western world. Despite advances in early detection and standard treatment, NSCLC is frequently diagnosed at an advanced stage and therefore patients have a poor prognosis. However, its heterogeneity provides ample opportunity for multiple treatment approaches and target pathways. Considerable progress has been made in identifying novel targets, leading to a growing number of treatment options. Overall survival (OS) may not always be the most appropriate primary end point for assessment of efficacy, as it is likely that patients with NSCLC will receive multiple lines of therapy during their treatment. Additionally, crossover appears as an ethical necessity to many investigators if molecular targeted agents display outstanding early efficacy. While improving OS remains the goal for clinicians, progression-free survival (PFS) is increasingly being utilised as an alternative end point. In this article, we will evaluate the value of PFS as a primary measure of efficacy for advanced NSCLC, compare the clinical situation with that in other solid malignancies and review the growing number of treatment options for NSCLC.