The field of synergistic combinations of antibiotics is extremely broad and mostly has been explored in vitro. Some fixed combinations were successfully developed commercially. A few combinations were tested in animal models, and a smaller number was studied in human patients. Any practitioner in infectious diseases has some individual cases, published or unpublished, which add some evidence to the role of synergistic combinations in difficult therapy problems--either on the side of the patient when immunosuppressed or on the side of the bacterial strain, when multiply resistant. MRSA, VISA, E. faecium resistant to penicillin G and highly resistant to aminoglysocides and to vancomycin, P. aeruginosa resistant to ceftazidime and imipenem, and Acinetobacter baumani resistant to imipenem are some of the bacterial strains dangerous for the patient and the hospital, which trigger the imagination of the microbiologist and physician to find a satisfactory treatment. On the side of the drug industry, the increasing knowledge of resistance mechanisms and of synergistic mechanisms may open some new approach, such as efflux inhibitors, a membrane-active compound that can be combined with a partner antibiotic. Antagonism between antibiotics would be worthwhile to study because it likely contributes to the disadvantages of the inappropriate use of antimicrobial combinations.