Preservatives in eye drops, while not always necessary, can lead to undesirable effects. Developing preservative-free solutions demands special measures for sterility, utilizing multidose or monodose primary packaging. This review explores the merits and drawbacks of these packaging types. A literature search on PubMed, Google Scholar, and EMBASE until December 2023, using MESH terms, yielded 28 studies on multidose ampoules and 24 on monodose packaging. Heterogeneous data revealed advantages and disadvantages concerning patient use and manufacturing. Chronologically presenting the development of eye drop packaging, this study finds Droptainer® simple but unable to maintain sterility. Comod®, 3K®, ABAK®, Novelia®, and Ophthalmic Squeeze Dispenser show high sterility probability, with Comod® and ABAK® having a contamination risk. Novelia® excels with long-term sterility and better control. Ophthalmic Squeeze Dispenser, FDA-approved, boasts a smaller carbon footprint. Unit-dose systems preserve sterility and offer design flexibility. Proposing an alternative, blister technology maintains sterility, is convenient and safe, and holds promise for recycling. This comprehensive assessment aids in understanding the evolving landscape of eye drop packaging, emphasizing the importance of sterility, convenience, and environmental impact.