Purpose of Review: Neoadjuvant systemic therapy (NST) has become a valuable treatment approach for women with large operable and locally advanced breast cancers by lessening the extent of surgery required to adequately resect the primary tumour. As molecular subtyping has evolved, the development of highly efficient systemic and targeted therapies has resulted in a marked improvement in pathologic complete response (pCR) rates in specific breast cancer subtypes. As a result, breast surgeons are often performing surgery on the breasts that contain no tumour cells. Thus, the notion of de-escalating or avoiding surgery after neoadjuvant treatment has re-emerged. Recent Findings: Retrospective series evaluating omission of surgery in women who demonstrate complete clinical response to NST suggest a trend towards increased rates of locoregional recurrence but predate the use of modern, targeted regimens. To be able to avoid surgery, it is critical to have the tools to accurately detect residual tumour disease and predict pCR after NST. Breast imaging including the recent addition of breast MRI has not sufficiently accurately predicted which patients will demonstrate pathologic complete response following NST. The combination of modern radiologic evaluation with image-guided tumour bed biopsies represents a potentially novel method towards selecting patients who could safely avoid surgical resection. Summary: This article reviews the current evidence supporting the elimination of surgery in selected patients, and discusses ongoing and future trials that address the possibility of a non-operative approach in women with early-stage breast cancer.