This talk presented a brief overview of what psychedelics are, and several signiﬁcant events in this ﬁeld in the past four decades. A comparison will be made between molecular structures, and how they were related to the structure of the neurotransmitter serotonin. The receptors that have been identiﬁed as targets for psychedelics were discussed, and their brain localization noted, followed by a brief description of where the receptors are located, and what happens inside the cell after the receptor is activated by a psychedelic. Comments included about the different intracellular signaling pathways that can be activated, and which one(s) may be important for altering consciousness. A diagram of connectivity between key brain regions was discussed, which will show how some of the effects of psychedelics may be induced. Particular note will be made of the difﬁculty in identifying psychedelic molecules in the absence of human experimentation, which is illegal. There will then be a discussion of the use of drug discrimination to identify “LSD-like” molecules, and an example from the author’s laboratory of the use of rigid analogues to identify important structural features of molecules such as LSD. Finally, a discussion was presented of the unique psychopharmacology of LSD, which occurs in two time-dependent phases, and the hypothesis that LSD may be converted in the body into an active metabolite that may be responsible for this time-dependent activity.