Over the past decade, non-fermenting Gram-negative bacteria have emerged as important opportunistic pathogens in the increasing population of patients who are immunocompromised by their disease or medical treatment. These bacteria are assisted by their ubiquitous distribution in the environment and have a propensity for multiple, intrinsic or acquired drug resistance. The infections that they cause now pose significant problems in terms of treatment and infection control, whilst the commonly observed rapid emergence of bacterial resistance to new antimicrobial compounds raises concerns regarding the clinical lifespan of these agents. Studies are urgently required to assess whether combination therapy can improve the long-term utility of new drugs in the treatment of patients infected with non-fermenters.