Major depressive illness is associated with significant costs for both the patient and health care systems. Against a background of limited resources, clinical efficacy cannot be regarded as the sole requirement in justifying innovative therapy. New therapies must establish both clinical and economic effectiveness. Even supposing that clinical trials offer the best vehicle for demonstrating such characteristics, trial data are not always in a form which enables cost-effectiveness to be investigated. There appears to be widespread agreement that patients should continue to receive active medication for a period of time, following an initial episode of depression. For the purposes of this paper, it is taken as axiomatic that such treatment would be based on selective serotonin reuptake inhibitors (SSRIs). The costs and consequences of the prophylactic use of SSRIs is investigated by simple modelling methods which enable several key parameters to be concurrently varied. The model simulates two alternative treatment strategies—a 'watchful waiting' approach in which patients are actively treated for depression once it reemerges; a prophylactic in which all patients received SSRIs following their initial episode of depression. The average cost per symptom-free patient is estimated to be 271, under the first strategy and between 474 and 389, under the second strategy. The results of this modelling exercise indicate that a strategy of maintaining patients with a known history of depression for a 12 month period on SSRIs. results in an increased number of patients who are symptom-free. Assessing the cost-effectiveness of such a strategy rests ultimately with the comparison of marginal costs and benefits. Although the revenue implications of a prophylactic treatment strategy are clearly significant, it may well be the case, that both psychiatrists and patients share the view that the costs are wholly justified in terms of the additional benefits for patients who avoid recurrence or relapse of their depression.