The New Delhi Metallo-β-lactamase (NDM) resistance mechanism in Enterobacteriaceae threatens to render serious Gram-negative infections untreatable. The NDM-1 enzyme hydrolyses all available penicillin, cephalosporin and carbapenem antibiotics, and is commonly accompanied by additional resistance mechanisms to multiple antibiotic classes. Initially identified as a significant healthcare risk on the Indian sub-continent, it has rapidly become a global problem, posing significant diagnostic and management challenges. Here we report the first laboratory-confirmed case of NDM-1 in South Africa.