Whereas in the past primary systemic therapy (PST) was rather used for other tumor entities or was limited to the use in inoperable breast cancer, treatment of operable stages is being increasingly investigated. After the proof of equivalency between PST and adjuvant chemotherapy, numerous trials have been conducted. PST enables testing of in vivo chemosensitivity; thus, treatment can be monitored by tumor response. Insufficient responders can be switched to non-cross-resistant concepts to avoid administration of ineffective drugs and try to achieve improvement of survival for these patients. The reduction of tumor size not only increases the rate of breast-conserving therapy, but has predictive value for the further course of the disease. Especially pathohistological complete remission is a good surrogate marker for improved survival and the goal of modern protocols in the preoperative setting. Actively recruiting trials (e.g. trials of the AGO PREPARE and TECHNO) integrate modern concepts of treatment like dose-dense, dose-intensified, sequential therapy and tumor targeting with trastuzumab in PST. Eligible patients should be recruited in ongoing trials to further elucidate the role of PST in primary breast cancer. Evaluation of predictive factors and correlation of therapy response to the genetic profile of the tumor with modern technologies will allow improved selection of patients with increasingly tailored therapy.