Breast cancer is a complex disease whose molecular mechanisms are not completely understood. Developing target therapies is a promising approach. Therefore, understanding the biological behavior of the tumor is a challenge. Tissue biopsy in the metastatic setting remains the standard method for diagnosis. Nevertheless, it has been associated with some disadvantages: It is an invasive procedure, it may not represent tumor heterogeneity, and it does not allow for treatment efficacy to be assessed or early recurrences to be detected. Analysis of circulating tumor DNA (ctDNA) may help to overcome this as it is a non-invasive method of monitoring the disease. In early-stage disease, it can detect early recurrences and monitor tumors' genomic profiles, identifying the emergence of new genetic alterations which can be related to tumor-acquired resistance. In the metastatic setting, the analysis of ctDNA may also allow for the anticipation of clinical and radiological progression of the disease, selection of targeted therapies, and for a photogram of tumor heterogeneity to be provided. It may also detect disease progression earlier in locally advanced tumors submitted to neoadjuvant treatment, and identify minimal residual disease. ctDNA analysis may guide clinical decision-making in different scenarios, in a precision medicine era, once it acts as a repository of genetic tumor material, allowing for a comprehensive mutation profiling analysis. In this review, we focused on recent advances towards the implementation of ctDNA in a clinical routine for breast cancer.