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In recent years, breast cancer treatment has become increasingly individualized. Circulating tumor cells (CTCs) have the potential to move personalized medicine another step forward. The prognostic relevance of CTCs has already been proven both in early and metastatic breast cancer. In addition, there is evidence that changes in CTC numbers during the course of therapy can predict treatment response. Thus, CTCs are a suitable tool for repeated treatment monitoring through noninvasive liquid biopsy. The next step is to evaluate how this information can be used for clinical decision making with regard to the extension, modification, or abandonment of a treatment regimen. This review will summarize the completed and ongoing clinical trials using CTC number or phenotype for treatment decisions. Based on current knowledge, CTCs can be regarded as a useful prognostic and predictive marker that is well suited for both risk stratification and treatment monitoring in breast cancer patients. However, there is still the need to provide sufficient and unequivocal evidence for whether CTCs may indeed be used to guide treatment decisions in everyday clinical practice. The results of the ongoing trials described in this review are eagerly awaited to answer these important questions.