Recent advances in molecular medicine and high-throughput sequencing technologies have achieved major cancer strategies and therapeutics over the past decades. For example, identification of oncogenic EGF receptor mutations that are present in up to 20% of lung adenocarcinoma patients confer exquisite sensitivity to EGF receptor inhibitors. However, currently known 'druggable' targets are enriched in the subgroup of adenocarcinomas and individuals who have never smoked. We present an overview of FGFs and FGF receptor (FGFR) signaling in cancer, and the role of FGFR1 as a novel druggable target in lung squamous cell carcinoma. FGFR1 amplification in lung squamous cell carcinoma is required for the survival of FGFR1-amplified cell lines. Currently, clinical reagents that target the FGFs and FGFRs are being developed accordingly. This review focuses on the emerging role of FGFR1 as a therapeutic target in lung squamous cell carcinoma and reviews current agents that are in clinical development for the treatment of FGFR-dependent cancer.