Numerous systemic medications have a potential ocular toxicity leading to permanent visual loss. Physiopathologic mechanisms associated with these toxic effects are yet unclear and, besides discontinuation of the drug, when possible, there is no current validated treatment once visual loss is present. Prevention lies on an awareness of potential risks of both the patient and the practitioner, a constant evaluation of the risk/benefice ratio of any treatment and, for some drugs, regular visual evaluations according to now more standardized protocols. In that respect, a tight link between the ophthalmologist and the referring practitioner is critical. Among oculotoxic drugs, anti-malarial treatment represents the most commonly prescribed. A better recognition of clinical characteristics of ocular toxicity along with progress in functional and structural evaluation of the visual system has modified follow-up protocols to obtain the earliest detection but a better knowledge in toxic mechanisms is still necessary.