Homeopathy might be employed for the prevention of epidemic diseases (homeoprophylaxis) provided remedies are selected on an individual basis in compliance with the ‘principle of symptom-based similitude’ and according to the totality of symptoms peculiar to a given epidemic (remedy of the ‘epidemic genius’ or ‘genus epidemicus), as countless examples in the literature show. The use of nosodes for the prevention of epidemic diseases (isoprophylaxis), i.e., selected based on the ‘principle of etiological identity’ with full neglect of symptom-based individualization and pathogenetic trials, is not supported by the homeopathic epistemological model. As long as there are no reliable scientific evidences attesting to its efficacy and safety, ‘isopathic immunization’ might not be indicated as a regular replacement of classical immunization, as it would mean a transgression of the bioethical principles of beneficence and non-maleficence. Although many homeopathic practitioners systematically indicate that practice, it is condemned by homeopathic institutions worldwide. In this article, I elaborate on epistemological, ethical and scientific features of these disparate approaches to prophylaxis, which I had summarily addressed in a previous review.