Community-acquired strains of methicillin-resistant Staphylococcus aureus (MRSA) have become a common cause of skin and soft tissue infections in the United States. These infections sometimes require treatment with antibiotics, and with the increasing resistance of pathogens to these agents, choosing the appropriate drug can be difficult. In lactating women who develop these infections, selecting an antibiotic is even more challenging, as clinicians need to be aware of risks to the infant from the drug excreted during lactation. To our knowledge, no review has addressed the safety of antibiotics in breastfeeding infants when the drugs are used to treat maternal skin and soft tissue infections from MRSA. Thus, we performed a literature search of the PubMed-MEDLINE and EMBASE databases (1974-March 2009), reviewed reference citations from identified publications, researched antibiotic prescribing information, and corresponded with drug manufacturers. Case reports, case series, and both in vivo and in vitro clinical trials were evaluated for the following antibiotics: clindamycin, daptomycin, linezolid, quinupristin-dalfopristin, rifampin, tetracycline, doxycycline, minocycline, tigecycline, trimethoprim-sulfamethoxazole, and vancomycin. Information for the newer antibiotics (linezolid, quinupristin-dalfopristin, tigecycline, and daptomycin) was limited. Despite heterogeneity in the data for the older antibiotics (clindamycin, rifampin, tetracyclines, trimethoprim-sulfamethoxazole, and vancomycin), all appear to be relatively safe in the minimal quantities nursing infants ingest through breast milk. Although the risk to infants seems to be relatively low for most of the agents we explored, the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection.