There are six major types of topical IOP-lowering drugs for glaucoma, and there have been as many as 56,000 different types of medication regimens. The rational use of medication is crucial, but there are two core issues: one is the establishment of the target IOP, and the other is the selection of first-line drugs. The target IOP is focused on the height of a single value, but also includes the fluctuation of IOP day and night. Overall, the lower and less volatile the level of IOP, the better the safety for the optic nerve. For every 10 mmHg reduction in IOP, the risk of optic nerve damage can be reduced by 10%. The clinical approach should be “individualized”, taking into account the baseline IOP level, the established degree of optic nerve damage, life expectancy, family history, history of high myopia, and history of diabetes. Generally, a reduction of 25% or more of the baseline level, or a reduction to less than 18 mmHg, is required. The overall trend in first-line medication use shows that prostaglandin analogs are gaining increasing importance. They lower IOP by increasing atrial aqueous drainage through the uveoscleral pathway. Because of their efficacy, safety, and frequency of use, prostaglandins have gradually replaced beta-blockers as the only first-line agents in recent years.