There is a consensus that molecular testing of the lung carcinoma should be the standard of care in the clinical management of patients with lung carcinoma. Recent practice guidelines in oncology and pathology recommend that all advanced and metastatic non-small-cell lung carcinoma with adenocarcinoma histology undergo biomarker testing for epidermal growth factor receptor gene (EGFR) mutations and anaplastic lymphoma kinase gene (ALK) rearrangements. Other types of non-small-cell carcinoma may be considered for such testing if they occur in never-smokers. The landscape of targetable biomarkers in non-small-cell carcinoma is changing rapidly, and demand for clinical testing beyond EGFR mutations and ALK gene rearrangements is increasing. Many patients may test positive for other ‘drivers’. As a result, they may be treated with approved biomarker-driven therapies or may be eligible to receive investigational agents in clinical trials. This creates challenges for treating physicians and pathologists such as obtaining sufficient tissue for molecular testing and standardisation of molecular testing in clinical laboratories. This review will focus on the most important lung carcinoma biomarkers predictive of response and will discuss proposed routine molecular testing in clinical practice.