Summary A wide range of topical ophthalmic drugs is available for use to provide a complete eye examination or a decrease in intraocular pressure or optimum conditions for many surgical procedures, but administration of these drugs is not free from the risks of serious adverse events. Most of the ophthalmic topical drugs show their effects via adrenergic or cholinergic receptors and systemic side effects of these drugs generally occur due to systemic absorption and overdose/toxicity. There are also other contributing factors such as age and related physiology of the patients or co-morbidities or previously prescribed medications. Therefore, one should be aware of the possible adverse reactions to topical ocular drugs and question the accompanying disorders and current medications of the patients inclusively to prevent and manage deleterious effects observed due to concomitant disorders and interaction between drugs.