Resistance to antibiotics continues to rise and few new therapies are on the horizon. Honey has good antibacterial activity against numerous microorganisms of many different genera and no honey-resistant phenotypes have yet emerged. The mechanisms of antimicrobial activity are just beginning to be understood; however, it is apparent that these are diverse and often specific for certain groups or even species of bacteria. Manuka honey has been most thoroughly characterized and is commercially available as a topical medical treatment for wound infections. Furthermore, since most data are available for this honey, there is a considerable focus on it in this review. It is becoming evident that honeys are more than just bactericidal, as they impact on biofilm formation, quorum sensing and the expression of virulence factors. With this in mind, honey represents an attractive antimicrobial treatment that might have the potential to be used alongside current therapies as a prophylactic or to treat wound infection with multidrug-resistant bacteria in future.