Often in clinical practice, dose modifications in the form of dose reductions or delays are warranted in response to treatment-related toxicity with systemic therapy administration [1,2]. However, this practice may raise concern about its impact on therapeutic benefit. Current guidelines from the National Comprehensive Cancer Network favor administration of systemic therapy (depending on the line) for patients with advanced-stage non-small-cell lung cancer (NSCLC) in good performance status, independent of their age. NSCLC clinical trials have primarily focused on testing new regimens rather than evaluating the impact of maintaining the delivery of dose and schedule of standard chemotherapy regimens. Overall survival (OS) is the primary measure of treatment efficacy, but other end points, such as progression-free survival (PFS) and clinical benefit, should be considered in advanced disease. Even with the recent development of several active molecularly targeted agents for the treatment of NSCLC, systemic cytotoxic chemotherapy still plays a role in disease palliation. In this editorial, we review contemporary clinical trials of platinum-doublet chemotherapy comparing dose and schedules, evaluating their impact on survival and tolerability, and the potential impact these may play in routine clinical practice.