In only few years, circulating tumor DNA (ctDNA) in breast cancer has moved from purely fundamental research to nearby daily use for treatment selection and drug-resistance assessment. Indeed, technical advances and widespread use of next-generation sequencing or digital PCR allowed for detection of very low amount of tumor DNA in bloodstream. The use of ctDNA as liquid biopsy able either to monitor tumor burden under treatment or to overcome tumor heterogeneity and identify potential targetable drivers. Time has come to define how ctDNA can be implemented for early or metastatic breast cancer management. Data from retrospective analyses of prospective trials have recently highlighted the potential advantages but also the limitations of ctDNA, in particular for patients under endocrine therapy.