Testing for antimicrobial interactions has gained popularity in the last decade due to the increasing prevalence of drug-resistant organisms and limited options for the treatment of these infections. In vitro combination testing provides information, on which two or more antimicrobials can be combined for a good clinical outcome. Amongst the various in vitro methods of drug interactions, time-kill assay (TKA), checkerboard (CB) assay and E-test-based methods are most commonly used. Comparative performance of these methods reveals the TKA as the most promising method to detect synergistic combinations followed by CB assay and E-test. Various combinations of antimicrobials have been tested to demonstrate synergistic activity. Promising results were obtained for the combinations of meropenem plus colistin and rifampicin plus colistin against Acinetobacter baumannii, colistin plus carbapenem and carbapenem plus fluoroquinolones against Pseudomonas aeruginosa and colistin/polymyxin B plus rifampicin/meropenem against Klebsiella pneumoniae. Antagonism was detected in only few instances. The presence of synergy or antagonism with a combination seems to correlate with minimum inhibitory concentration of the agent and molecular mechanism involved in the resistance. Further studies need to be conducted to assess the utility of in vitro testing to predict clinical outcome and direct therapy for drug-resistant organisms.