Immediate breast reconstruction relies on healthy mastectomy flaps for success. Tissue perfusion of these mastectomy flaps is dependent on multiple patient-, operative-, and surgeon-specific factors, which must be optimized. Unfortunately, tissue perfusion is also notoriously difficult to accurately assess and investigate. In this review, we discuss the importance of tissue perfusion in successful reconstructive breast surgery with an emphasis on perfusion assessment and techniques to ensure that anatomic mastectomy flap perfusion is maintained for immediate breast reconstruction after mastectomy. Preoperative and patient-specific factors should be considered with operative plans modified to minimize ischemic risk. Intraoperatively, incision planning and mastectomy dissection will dictate skin flap perfusion. Most importantly, mastectomy dissection in a plane at the breast capsule will maximize preservation of the subdermal plexus and subcutaneous perforators that supply the breast skin envelope while also maximizing oncologic parenchymal resection. Such anatomic dissection has been demonstrated to decrease risk of ischemic complications in immediate breast reconstruction. Postoperatively, any potential or actual areas of impaired perfusion and ischemia must be diagnosed appropriately and managed proactively to ensure a successful reconstruction. It is also important for surgeons to be aware of imaging modalities and adjunctive technologies that can help promote and assess optimal mastectomy flap tissue perfusion. Plastic surgeons and breast surgeons must actively and collaboratively work together to ensure their mutual goals are met, and optimal outcomes are attained for patients undergoing immediate breast reconstruction after mastectomy.