Implant-based breast reconstruction accounts for more than 70% of all breast reconstructions, and breast augmentation is the most commonly performed cosmetic operation annually. The clinically significant impact of infection and capsular contracture after breast implant surgery has brought clinicians to create infection reduction protocols for both oncologic and cosmetic operations alike. The use of triple-antibiotic saline irrigation has become a recommended intraoperative maneuver within these protocols to minimize surgical site infections, but the constituents of the irrigation, its individual efficacy, and the acceptability of including povidone-iodine within irrigation recipes have been debated. This review will investigate the microbiological data behind the selection of the constituents of triple-antibiotic saline. In vitro testing of the effectiveness of topical antibiotics used in saline irrigation against microorganisms responsible for breast implant infection is reviewed. Clinical data are presented describing the impact of triple-antibiotic saline on implant infection and capsular contracture after cosmetic and reconstructive surgery.