Modern sophisticated archeometric instruments are increasingly capable of detecting the presence of psychoactive plant sources in archeological contexts, testifying the antiquity of humanity’s search for altered states of consciousness. The purpose of this article is to provide a general picture of these findings, covering the main psychoactive plant sources of the world, and identifying the most ancient dates so far evidenced by archeology. This review is based on the archeological literature identifying the presence of psychoactive plant sources, relying on original research documents. The research produced two main results: (a) a systematization of the types of archeological evidence that testify the relationship between Homo sapiens and these psychoactive sources, subdivided into direct evidence (i.e., material findings, chemical, and genetic) and indirect evidence (i.e., anthropophysical, iconographic, literary, and paraphernalia); and (b) producing a list of the earliest known dates of the relationship of H. sapiens with the main psychoactive plant sources. There appears to be a general diffusion of the use of plant drugs from at least the Neolithic period (for the Old World) and the pre-Formative period (for the Americas). These dates should not to be understood as the first use of these materials, instead they refer to the oldest dates currently determined by either direct or indirect archeological evidence. Several of these dates are likely to be modified back in time by future excavations and finds.