Carbapenems are broad-spectrum β-lactam antibiotics that act by inhibition of cell wall synthesis. Various families of carbapenemases comprising numerous members have been identified, which may be plasmid or chromosomally encoded. More than one mechanism of carbapenem resistance (carbapenem-resistant enterobacteriaceae, CRE) has been identified with sporadic reports of CRE infection across the world. Appearance of carbapenem resistance in enterobacteriaceae is worrying as infection with these organisms has high mortality rates with fewer treatment options, which are expensive and have more adverse effects. Colistin and tigecycline are the currently available options for treatment of CRE infections. Carbapenem resistance in the enterobacteriaceae and other Gram-negative bacteria may be due to carbapenemase-mediated or noncarbapenemase-mediated mechanisms. In our review, we have compared different forms of carbapenem resistance and discussed issues related to susceptibility testing, treatment options, and subsequent clinical outcome.