Surgical resection of the primary tumor is a necessary and effective treatment for breast cancer patients. For various reasons discussed, we believe that the short postoperative period is critical for eliminating minimal residual disease (MRD), thus markedly impacting long term survival. Unfortunately, both animal and human studies have shown that surgery induces suppression of anti-metastatic cell-mediated immunity (CMI) at this critical period, which is suggested to worsen patients' prognosis. In this review we examine different aspects of the surgical procedure that cause immunosuppression (e.g., anesthesia and tissue damage), discuss their mediating humoral and cellular mechanisms, and suggest prophylactic interventions feasible in cancer patients to avoid postoperative suppression of CMI. The use of the suggested interventions has been shown to significantly reduce postoperative metastasis in animal models, including mammary adenocarcinoma, and initial data suggest similar efficacy in breast cancer patients. We believe that our recommended prophylactic interventions can easily be applied by health-care practitioners and hold promise in reducing long-term recurrence and metastasis in cancer patients.