Lung cancer is the leading cause of cancer-related mortality. Improved understanding in the molecular biology and genetics of lung cancer has resulted in the identification of individual genes, gene expression profiles, and molecular pathways that may be useful for clinical management decisions. We focused on recent molecules and platforms under evaluation for implementation into clinical decision making. Prognostic molecular parameters are defined as markers that impact overall outcome in terms of survival independent of therapeutic interventions. Predictive molecular parameters are defined as markers that impact therapeutic efficacy. Several molecules and profiles are emerging with promising utility as predictive and prognostic parameters in non-small cell lung cancer independent of the standard clinical parameters, such as stage, performance status, and gender. These include the genes ERCC1, RRM1, and BRCA1, which are involved in nucleotide metabolism and DNA damage repair, epidermal growth factor receptor, which is involved in cell proliferation and survival, and oligonucleotide expression array profiles, which are signatures of global gene expression associated with specific tumor phenotypes.