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The recent resurgence of tuberculosis (TB) has led to calls for improvements in isolation facilities. This paper presents the findings of a literature review and an evaluation study of current design guidelines and performance expectations for isolation room mechanical ventilation systems. The inter-zone airflows in a typical isolation ward were modelled to unveil the issues that are critical to isolation performance and to determine the practicality of the recommendations in the literature. It was found that the air leakage through partitions and door gaps would be highly undesirable. With adequate supply and exhaust flow rate differences, and practicable construction quality, differential pressures of up to 7 Pa or higher should be achievable between isolation rooms and adjacent areas.