Challenges of drug combinations Combinations of antibiotics are used to treat intractable infections such as methicillin-resistant Staphylococcus aureus . Clinically, however, drugs tend to be used empirically, and results can be contradictory. Liu et al. translated observations made in vitro to patient samples to understand the role of antibiotic tolerance in promoting or suppressing resistance when drug combinations are used (see the Perspective by Berti and Hirsch). Although bacterial populations exposed to multiple antibiotics can develop tolerance to multiple drugs, one drug in a combination may be able counter resistance to a partner drug and provide effective therapy. However, if tolerance has already emerged to one drug, the combination may end up promoting the transmission of resistance to a partner drug. Science , this issue p. 200 ; see also p. 141