The treatment of localized breast cancer often requires the use of surgery, radiation, and chemotherapy. The optimal sequencing of these treatments remains controversial. Although randomized studies have not found an improvement in survival with the use of neoadjuvant chemotherapy, a higher percentage of patients can undergo breast conservation. This clinical setting also allows us the unique opportunity to measure in vivo response to a select drug or drug combination. While there have been many retrospective studies looking at prognostic markers of response, there have been very few prospective studies developing markers that predict ultimate outcome from a specific drug or drug combination. This review discusses some of the newer technologies being used to develop predictive markers of therapeutic response. Proteomics is the study of the complete set of proteins expressed in a cell. It is a powerful tool to compare two different samples. Serial biopsies that compare the protein profile before and 24 hours after a cycle of chemotherapy may allow us to determine particular protein profiles that predict for ultimate clinical outcome.