Circulating tumour DNA (ctDNA) analysis has the potential to advance precision medicine. The epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) single gene assays in plasma cell free DNA are being used for selecting patients with metastatic lung and breast cancer for treatment with EGFR and PIK3CA inhibitors, respectively. More recently, multigene assays have been approved by the Food and Drug Administration as companion diagnostics for the selection of patients that may benefit from specific targeted therapies. Moreover, ctDNA may allow a noninvasive monitoring of tumour genotype and treatment response. Potential future applications include systemic treatment of patients with ctDNA relapse and early cancer detection.