Building occupants are exposed to complex mixtures of air pollutants including many volatile organic compounds (VOCs). A recent review summarized the central tendency and upper limit indoor VOC concentrations measured in North American residences and office buildings since 1990. Although this database is limited in many respects, it serves as a useful starting point for evaluating the potential health and comfort effects of indoor VOC exposures. Excluding cancer and birth defects, the primary concern is chronic inhalation exposure to toxicants that can cause serious health problems. Additionally, building occupants react to the quality of indoor air through their sensory perceptions and frequently experience unpleasant odors and irritation of the eyes and upper respiratory tract. In this paper, we conduct a simple screening-level assessment of indoor VOC concentrations. We compare measured VOC concentrations to published odor thresholds, sensory irritation levels derived for the general population, and noncancer chronic health guidelines. Hazard quotients are individually calculated for these three effects by dividing maximum or derived 95th percentile VOC concentrations by our selected best estimates of guidance levels for the general population. These results provide a basis for broadly classifying commonly encountered VOCs into groups according to the likelihood that they will produce effects among building occupants. This methodology shows that only a small number of the more than 100 reported VOCs exceed levels that are likely to be of concern with respect to the health and comfort endpoints considered. Although data is lacking for a number of odorous compounds potentially present in buildings, the results indicate that carboxylic acids, higher molecular weight aldehydes and less volatile aromatic hydrocarbons are most likely to be perceived by olfaction and that there is more probability of detection in residences than in offices. Sensory irritation levels were approached or exceed by only a very small number of relatively potent, reactive VOCs. Of these, acrolein was by far the most potent irritant. Although more detailed consideration of the underlying toxicological data is needed, the results suggest that only a small number of commonly measured VOCs, when considered singly, are likely to produce serious irreversible health effects not associated with cancer. These compounds include lower molecular weight aldehydes, and several aromatic hydrocarbons. Again, acrolein stands out as the most potent compound. Based on these results, we recommend that studies to characterize indoor VOC concentrations and exposures focus their resources on compounds that are most likely to impact occupants as determined by the study objectives. For a very few compounds, such as acrolein and formaldehyde, the evidence based on sensory irritation and chronic toxicity appears sufficient to warrant efforts to reduce and control sources of these compounds in buildings.