BACKGROUND Cilia in the human respiratory tract play a critical role in clearing mucus and debris from the airways. Their function can be affected by a number of drugs or other substances, many of which alter ciliary beat frequency (CBF). This has implications for diseases of the respiratory tract and nasal drug delivery. This article is a systematic review of the literature that examines 229 substances and their effect on CBF. METHODS MEDLINE was the primary database used for data collection. Eligibility criteria based on experimental design were established, and 152 studies were ultimately selected. Each individual trial for the substances tested was noted whenever possible, including concentration, time course, specific effect on CBF, and source of tissue. RESULTS There was a high degree of heterogeneity between the various experiments examined in this article. Substances and their general effects (increase, no effect, decrease) were grouped into six categories: antimicrobials and antivirals, pharmacologics, human biological products, organisms and toxins, drug excipients, and natural compounds/other manipulations. CONCLUSIONS Organisms, toxins, and drug excipients tend to show a cilioinhibitory effect, whereas substances in all other categories had mixed effects. All studies examined were in vitro experiments, and application of the results in vivo is confounded by several factors. The data presented in this article should be useful in future respiratory research and examination of compounds for therapeutic and drug delivery purposes.