Antimicrobial resistance of Gram-negative bacteria is a major concern, and no new classes of antibiotics that are effective against this type of bacteria have been discovered since the 1960s. During the last decades, multiple approaches have been developed to combat such bacterial resistance. However, the combination of antibiotic resistance mechanisms by bacteria and the limited number of effective antibiotics available, decreases the number of interventions for the treatment of current bacterial infections. The solution to emerging antibiotic resistance will likely involve new therapies or new classes of antibacterial agents. For a few years now, there was a real interest in the design and synthesis of hydrazones possessing an azometine -NHN=CHproton and constituting an important class of compounds for new drugs development as anticonvulsants, antidepressants, antitumoral agents. In this context, the design and antimicrobial evaluation of hydrazone derivatives have constituted one of the new strategies developed to fight bacterial resistance. As pointed out, the range of biological activities is very broad, and this review will deal exclusively with the synthesis and use of hydrazones as antimicrobial agents and will not cover the other biological properties already well depicted in literature. Thus, we will report herein the scope and limitation of such an approach providing numerous examples demonstrating structure-activity relationships and potent interesting antimicrobial activities against both fungi, Grampositive and/or Gram-negative bacteria.