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The Space Station Freedom (SSF), with a 30-year projected lifetime and a completely closed-loop Environmental Control and Life Support System (ECLSS), is perhaps the ultimate “Tight Building.” Recognizing the potential for the development of “Tight Building Syndrome” (TBS), and initiating actions to minimize possible TBS occurrences on SSF, requires a multidisciplinary approach that begins with appropriate design concerns and ends with detection and control measures on board SSF. This paper will present a brief summary of current experience with TBS on Earth. While many of the circumstances and methodologies garnered from investigating tight buildings on Earth are similar to those that might be encountered aboard SSF, the Station also presents a unique environment and a special set of constraints which will require an adaptation of previous protocols. Air contamination, including volatile organic compounds and microorganisms, will be the focus of the discussion.