Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative nosocomial pathogens commonly carry one carbapenemase gene conferring resistance to carbapenems and other beta-lactam antibiotics. However, increasing reports show that double-carbapenemase-producing (DCP) and even multi-carbapenemase-producing (MCP) bacteria are emerging in some parts of the world, diminishing further, in some cases, the already limited treatment options. In the present review, the up-to-date reports of DCP and MCP isolates are summarized and concerns regarding their emergence are discussed.