Implant-based reconstructions are increasingly utilized following mastectomy in the prevention and treatment of breast cancer. However, these implants are associated with a high rate of infection, which is a major complication that can lead to implant removal, delay in adjuvant radiation and chemotherapy, and increase in health care costs. Early clinical signs and symptoms of infection, such as erythema, warmth, and tenderness, are challenging to discern from expected postsurgical responses. Furthermore, when atypical features are present or the patient's condition does not improve on adequate antimicrobials, the clinician should be prompted to consider an alternative noninfectious etiology. Herein we highlight the key elements of the preventive, diagnostic, and multidisciplinary therapeutic approach to salvaging the infected breast implant; review several infectious disease mimickers; and provide many pearls of wisdom that the practicing clinician must be familiar with and be able to manage in an effective and successful manner.SummaryBreast implant-based reconstructive procedures after mastectomy has been historically associated with an elevated infection rate. Herein, we perform a comprehensive review on many key aspects on the prevention, diagnosis, treatment, and mimickers of these complex implant-related infections.