Since the first usage of antimicrobials, the burden of resistance among bacteria has progressively increased and has accelerated within the last 10 years. Antibiotic resistance genes were present at very low levels prior to the introduction of antibiotics and it is largely the selective pressure of antibiotic use and the resulting exposure of bacteria, not only in humans but also in companion and food animals and the environment, which has caused the rise. The increasing mobility across the globe of people, food and animals is another factor. Examples of this are the international pandemic of different genotypes of CTX-M extended-spectrum beta-lactamases (particularly CTX-M-14 and -15) and the emergence of the carbapenemase KPC-1 in both the USA and Israel. This review details examples of both the emergence and dissemination through different genetic routes, both direct and indirect selective pressure, of significance resistance in Staphylococcus aureus, Enterococcus species, Enterobacteriaceae and Pseudomonas/Acinetobacter. The response made by society to reduce resistance involves surveillance, reduced usage, improved infection control and the introduction of new antimicrobial agents. Although efforts are being made in all these areas, there is an urgent need to increase the effectiveness of these interventions or some bacterial infections will become difficult if not impossible to treat reliably.