Although the safety of phakic intraocular lenses (pIOLs) has been continuously improved over 70-years of development, high endothelial cell losses can occur even with current pIOL models. Numerous studies have demonstrated that the distance of a pIOL to the corneal endothelium plays a crucial role in the extent of endothelial cell loss. For this reason alone, higher endothelial cell loss tends to be observed with anterior chamber lenses than with posterior chamber lenses. Adequate preoperative anterior chamber depth is essential, at least for iris-fixed pIOLs, in order to ensure a safe distance from the endothelium. However, the anterior chamber becomes shallower with age and therefore it may be useful to consider patient age in the safety criteria. Although endothelial cell loss is generally low with current pIOL models, regular monitoring of the endothelial cell density remains essential due to large interindividual differences in patients with pIOLs. If the endothelial cell loss is greater than expected and the follow-up visits confirm the trend, the pIOL should be explanted without delay. The endothelial reserve should be considered on an individual basis by taking into account patient age, physiological endothelial cell loss, and loss due to further surgery. With careful indication and long-term patient care, pIOLs remain a safe treatment option.