Elucidation of the molecular events that underlie respiratory epithelium carcinogenesis still remains a largely unresolved issue. Various new therapeutic interventions are in advanced clinical testing or in daily clinical practice based on available preclinical findings. However, the complex molecular interplay that characterizes carcinogenesis requires further investigation to identify the pivotal factors and their interactions that might render the treatment of these malignancies more effective. Insulin-like growth factor-1 (IGF-1) network is a new important signalling cascade in lung carcinogenesis. Here, we integrate updated results that further support the significance of IGF-1 molecular circuitry in respiratory epithelium tumourigenesis, and pose future perspectives regarding its optimal use in the therapeutic field.