Secondary cataract or posterior capsule opacification (PCO) is still the most frequent long-term complication of cataract surgery. Tremendous advances have been made, especially during the last 10 to 15 years, in terms of surgical techniques and improvement of implant technology. However, the problem of proliferation and migration of lens epithelial cells (LECs) postoperatively has not yet been solved completely although we know that a sharp optic edge of intraocular lenses (IOL) combined with hydrodissection, complete overlapping of capsulorhexis and IOL-optic as well as capsular bending reduce PCO formation significantly. In the 1980 s, investigators like Hartmann et al. began with the application of pharmacological substances in-vitro in order to successfully prevent LECs from proliferating and migrating. Cytostatic drugs, steroids, non-steroidal antiphlogistics, adhesion inhibitors, heparin, lidocaine, suramin, immunotoxins, photodynamic therapy and osmotic effective solutions were tested. In several studies different drug delivery systems were investigated in order to provide a longer and more effective impact on LECs. However, the in-vivo use has been viewed critically since the selective targeting of LECs was not possible and serious damage to the surrounding tissue had to be considered. Recently, the development of the PerfectCapsule System for vacuum-sealed capsule irrigation allows the selective targeting of LECs inside the capsular bag. This survey gives an update on past, current and future means and trends to reduce or prevent PCO formation pharmacologically.