Continuous breast-feeding, an integral component of the postpartum period, is often threatened upon maternal initiation of antibiotics. The real risk of antibiotic use while breast-feeding must be carefully analysed with regard to all the variables that influence the extent of antibiotic distribution into breast milk, including breast milk composition, physicochemical properties of the antibiotic (molecular weight, lipid solubility, pH, protein binding), length of feeding, and maternal disposition. In addition, infant disposition, including ability to absorb, metabolize, eliminate, and tolerate any amounts of antibiotic, must also be considered prior to maternal administration of antibiotic. The milk to plasma (M/P) ratio is a frequently quoted parameter used to predict drug distribution into breast milk. However, its utility is questionable and often fraught with misinterpretation. An alternative approach when the amount of antibiotic concentration in breast milk is known (through clinical trials) is to calculate an estimated or expected infant drug exposure factoring in known/expected milk consumption, drug concentration and bioavailability. In this review, the following antibiotic classes and current literature regarding their distribution into breast milk are critically reviewed: beta-lactam antibiotics, fluoroquinolones, sulfonamides, macrolides, aminoglycosides, tetracyclines, nitrofurantoin, metronidazole, vancomycin, clindamycin and chloramphenicol. In the majority of instances, these antibiotics do not distribute into breast milk in sufficient concentrations to be of any clinical consequence in the breast-feeding infant.