Recent studies have defined the survival pathways activated by receptor tyrosine kinases that are critical in the transformation of human bronchial epithelial cells and in maintaining the survival of non-small cell lung cancer (NSCLC) cells. Protein kinase B (AKT) is one element of receptor tyrosine kinase signaling that is activated in bronchial premalignancy and NSCLC. Recent studies have shown that AKT cooperates with the stress kinase mitogen-activated protein kinase kinase 4 to maintain the survival of NSCLCs. These studies illustrate the importance of understanding the interactions between survival pathways and developing inhibitors to specific kinases that can be used alone or in combination in clinical trials for lung cancer prevention and treatment.