Orphan drugs are designed to treat rare diseases. Such diseases are life-threatening, cause chronic disability and have a low prevalence. Due to their low prevalence make, drug companies cannot easily recover their investments in research and new drug development, in spite of the usually high prize of orphan drugs. Therefore, decisions on orphan drugs financing should take into account several criteria. We aimed at describing and explaining various aspects relating to economical assessment of orphan drugs for rare disease treatment, and their impact on decisions on financing. Therapy efficiency and equity, orphan drug costs, cost-effectiveness ratio, and impact of such drugs on budget will be discussed. Orphan drug financing decisions do not depend on a sole criterion, such as cost-effectiveness ratio. If so, access to drug therapy would be denied to patients. When a single criterion is being uses, a conflict may develop with other criteria. In summary, orphan drugs that are reimbursed show how important other criteria (besides cost-effectiveness analysis) can be for decision-taking. Such criteria are impact on budget, clinical efficacy, and equity in financing and accessing decisions.