Infectious disease is an emerging threat that conservationists are ill-equipped to manage. The threat is greatest for small populations, which can be driven to extinction by virulent pathogens; these are usually generalist pathogens that ‘spill over’ from other host species, often domestic animals. Recent attempts at disease control have taken a variety of forms, some directed at threatened hosts themselves, and others involving reservoir hosts. Thus far, few such attempts have demonstrated clear benefits of intervention, often because they were ‘crisis management’ tactics allowing no comparison with untreated controls. Design of future strategies is hampered by a lack of basic information concerning the pathogens that represent serious threats, their epidemiology in multiple-host systems, and the vaccination or treatment protocols likely to be most effective under field conditions. In general, vaccination and treatment will be most valuable in tiny populations facing very high extinction risks. However, interventions that are poorly planned or under-funded have the potential to do more harm than good. In larger populations, or over larger areas, intensive management may be inappropriate, unsustainable, or simply impractical. In these circumstances, managing population size, structure or contact between host species could offer promising alternatives to intervention.