Aurora kinases (A, B, and C) are essential for spindle assembly, centrosome maturation, chromosomal segregation, and cytokinesis. Aurora kinases A and B are overexpressed in many cancers, including non-small-cell lung cancer and mesothelioma. Small-molecule inhibitors selective for aurora kinases have shown promising activity in preclinical tumor models. To date, phase I studies with aurora kinase inhibitors have shown that myelosuppression is the dose-limiting toxicity, and disease stabilization was achieved in a number of tumor types, including non-small-cell lung cancer. Phase II trials are under way in selected tumor types. This article reviews the biology of aurora kinases, their potential role in the treatment of lung cancer, and challenges in the clinical development of this unique class of antineoplastic agents.