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Exhaled breath analysis holds great promise for the development of noninvasive, frequently repeatable diagnostic and monitoring tools. For clinical breath analysis to advance beyond its current state, however, much closer multidisciplinary collaboration needs to be not only recognized but also effected. Therefore, this paper reviews the current state of clinical breath analysis from the perspective of the challenges the field faces medically (biomarker uncertainties, sampling methods, dynamics of exogenous compounds within the body, and standardization), technologically (the need for an affordable, user-friendly, real-time, point-of-care instrument for accurate identification of breath volatiles and their concentrations), biochemically (the need to link exhaled compounds with specific diseases by understanding the volatile products particular to relevant pathogenic processes), and in terms of data interpretation (quality, quantity, and complexity of data), collaboration (the need for a more integrated approach to breath analysis, including public health input), and development from research to accepted clinical use (funding challenges peculiar to the medical/technological interface, achieving standards of effectiveness and cost-effectiveness). Having thus increased awareness and aligned expectations among relevant disciplines, this paper provides a course of action for closer collaboration, better understanding, and more productive dialogue between these disciplines, including an iterative sensor development process that is integrated with clinical trials, formation of goals that transcend individual disciplines, creation of multidisciplinary research teams and a cross-disciplinary student exchange program, and collaborative funding options.