The history of the development of the quinolones is described from the first quinolone, nalidixic acid, via the first 6-fluorinated quinolone norfloxacin, to the latest extended-spectrum fluoroquinolones. The structural modifications made to the basic quinolone and naphthyridone nucleus and to the side chains have allowed improvements to be made such that the next group of fluoroquinolones after norfloxacin, exemplified by ciprofloxacin, had high activity against gram-negative species and a number of atypical pathogens, good-to-moderate activity against gram-positive species and were well absorbed and distributed. These compounds have been successfully used in the clinic for a decade and the size of the market has risen in recent years to only a little less than that for penicillins and macrolides. Notwithstanding the broad spectrum of these compounds, defects became evident. The growth in understanding of structure activity relationships with fluoroquinolones has enabled the development of even better compounds. The targets in fluoroquinolone research during the last few years include: improvements in pharmacokinetic properties, greater activity against gram-positive cocci and anaerobes, activity against fluoroquinolone-resistant strains, and improvements in activity against non-fermentative gram-negative species. The compounds developed in the recent years have fulfilled some but not all of these goals; improved bioavailability is one target achieved with most of the more recent compounds allowing for once-daily dosing. Gatifloxacin, moxifoxacin and trovafloxacin have all greatly improved the activity against gram-positive cocci, particularly pneumococci, and against anaerobes. They are not quite as active as ciprofloxacin against Enterobacteriaceae, and show no substantial improvements in activity against non-fermentative species. Clinafloxacin, gemifloxacin and sitafloxacin have even better activity against gram-positive cocci and are as active as ciprofloxacin against most gram-negatives, though gemifloxacin is less active than the other new compounds against gram-negative anaerobes. These three compounds do retain some activity against a number of ciprofloxacin-resistant species (gram-positive and gram-negative), but whether this activity will be adequate for clinical use is at present unclear. Both clinafloxacin and sitafloxacin contain a chloro substituent at position 8 of the quinolone nucleus. A halogen at this position in a number of compounds, though giving good activity, has also been associated with phototoxicity. Several fluoroquinolones have had to be withdrawn or strictly limited in their use post-marketing and in some cases no obvious relationship can be seen between the adverse effects and structural features, making this an area for urgent research.