Fluoroquinolones are an important class of synthetic broad-spectrum antibiotics. They display excellent activity against Gram-negative bacteria, and moderate activity against Gram-positive bacteria. The use of fluoroquinolones is wide spread, for both systemic and topical applications, for which prolonged release is highly desirable. To this end, we have assisted to the rise of cutting edge nanotechnologies that have been effective in achieving sustained drug delivery and formulations with improved performance. In addition, fluoroquinolones are essential tools in the treatment of multi-drug resistant diseases, such as tuberculosis. However, they have a small, but significant, potential for serious adverse effects, which should be carefully evaluated. Over the years, a consistent body of work on the structure-activity profile of fluoroquinolones has allowed for the development of various generations of these antibiotics, with new molecules still emerging to-date. This is the result of the permanent quest towards the discovery of new compounds that may be capable of reducing side effects and, especially, of evading the growing issues of antibiotic resistance. In particular, concerns exist over their excessive use and consequent release in the environment as one of the factors facilitating the insurgence of antibiotic-resistance. In this regard, a prolific area of research addresses the application of nanotechnologies to provide innovative solutions for the antibiotics' monitoring in, and removal from, the environment.