Objectives: The aim of this work is to describe standard and modern preservatives, pharmacopeic testing of antimicrobial effectiveness of preservatives and discuss preclinical and clinical safety aspects of their use in topical ophthalmic preparations. Materials and methods: Targeted literature search was done on MEDLINE / PubMed, Science Direct, Google search engine, website and database of Croatian Agency for Medicinal Products and Medical Devices, articles in the research journals, available documents of manufacturers and patents. The database searching of the scientific literature includes period up to October 2016. Results: A topical ophthalmic medicinal products are sterile pharmaceutical forms which are most often packaged in multidose containers containing a preservative, in a suitable concentration for the prevention of secondary microbial contamination of the drug. Long-term use of topical ophthalmic medicinal products can cause toxic ophthalmic side effects or allergy, but also iatrogenic diseases of the eye, and they may be caused by any excipient (e.g., preservative) or the active substance contained in an ophthalmic medicinal product.Benzalkonium chloride (BAK) is a preservative commonly used in topical ophthalmic medicinal products. Possible adverse effects of BAK depend on the duration and dose of application. With the aim of overcoming the disadvantages of BAK, modern preservatives or inovative packaging of topical ophthalmic medicinal products are being developed. Conclusion: Since the application of eye drops without preservatives has significantly less pronounced side-effects as compared to administration of the preserved eye drops, in patients with chronic diseases of the eye and / or with a damaged ocular surface it is advisable to apply eye drops without preservatives.