Preoperative administration of chemotherapy is a widespread treatment approach in early stage breast cancer whenever chemotherapy is indicated in principle. In addition, neoadjuvant treatment is today regarded as the preferred way of delivering systemic therapy in triple-negative and HER2-positive breast cancer. While preoperative chemotherapy allows for disease downstaging and increases breast conservation rates, achieving pathologic complete remission (pCR) is usually regarded as the most pertinent aim as pCR predicts for improved long-term outcome in high-risk breast cancer subtypes. A multitude of clinical trials therefore have focused on strategies to increase pCR rates. This short review summarizes outcomes of selected studies investigating the addition of further chemotherapeutic drugs or biologically targeted agents to standard regimens and provides an overview of novel strategies currently under clinical evaluation.