Oral and maxillofacial pain, inflammation, and associated pathologies have been documented since the beginning of recorded human history, and the use of plant materials from certain families for the relief of these disorders has paralleled this health care need. Humans discovered, through personal experimentation, that numerous plants and plantbased products placed into the oral cavity had the capacity to deliver diverse secondary metabolites and thereby elicit a variety of stimulant, medicinal, and hallucinogenic effects. Recent pharmacognostic research has confirmed the presence of medicinal compounds in several of these plants. Contemporary neurobiological and pathophysiologic research has illuminated the mechanisms and actions of numerous tissues, cell structures, TRP channels, mammalian peripheral and CNS receptors, actions responsive to plant-based and other natural compounds. Consequently, theories have emerged that propose a co-evolutionary relationship and functionality between natural products and the various mammalian cell membrane channels, receptors, and tissues. In this brief review, we will indicate some of the background relating to the contemporary views of the use of various plant-based products as analgesic and anesthetic agents for oral pain and inflammations and briefly discuss their mechanisms of action. An overview of the need for new, plant-based oral analgesic agents and for new experimental models for the discovery process from plant extracts will be described and some discussion will be offered regarding the potential for future research developments in this area of pharmacognosy.