Antibiotic resistance is now a linked global problem. Dispersion of successful clones of multidrug resistant (MDR) bacteria is common, often via the movement of people. Local evolution of MDR bacteria is also important under the pressure of excessive antibiotic use, with horizontal gene transfer providing the means by which genes such as bla(CTX-M) spread amongst different bacterial species and strains. Beta-lactamase production is a common resistance mechanism in Gram-negative bacteria, and the rapid dissemination of novel genes reflects their evolution under the selective pressure of antibiotic usage. Many Enterobacteriaceae now carry broad-spectrum beta-lactamases such as CTX-M, with particular genotypes associated with different geographical regions. The spread of these enzymes has compromised the clinical utility of a number of beta-lactam classes and with the spread of genes such as bla(KPC), carbapenems may be increasingly compromised in the future. High-level fluoroquinolone resistance (mainly caused by gyrA mutations) has also been shown to be associated with CTX-M and CMY-type enzymes, commonly due to co-carriage on conjugative plasmids of the gene for the aminoglycoside-inactivating enzyme AAC-6(1)-Ib-cr and qnr genes (which confer low-level resistance), allowing the easy selection of gyrA mutants in the host strain. Resistance in Gram-positive bacteria is also widely distributed and increasing, with the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) blurring the distinction between hospital and community strains. Antibiotic use and environmental factors all have a role in the emergence and spread of resistance. This article reviews some of the new mechanisms and recent trends in the global spread of MDR bacteria.