Purpose of reviewGram-negative bacilli (GNB) cause between 1% and 10% of infective endocarditis (IE). Most episodes are caused by microorganisms of the Haemophilus spp., Aggregatibacter spp. Cardiobacterium spp., Eikenella spp., and Kingella spp (HACEK) group. The frequency of IE caused by non-HACEK (GNB-IE) has increased in recent years. Uncertainties persist regarding its best medical treatment and the appropriateness and timing of surgical treatment. In addition, there are new drugs with activity against multiresistant microorganisms, of which there is little experience in this disease. We review this topic by answering the most frequently asked questions that arise among our colleagues.Recent findings HACEK microorganisms cause 1.5-2% of IE with only a 2% mortality. In contrast, non-HACEK GNB-IE accounts for 2.5-3% of all IE cases and is associated with nosocomial acquisition, advanced age, solid organ transplantation and 20-30% mortality. Drug addiction is important in areas with epidemic opioid abuse.