The concepts of "set" and "setting" are fundamental to understanding and optimizing the psychedelic experience. These terms, which emphasize the importance of one's mindset ("set") and the physical and social environment ("setting"), were observed by Al Hubbard during mushroom ceremonies in Mexico and were used as early as 1958 by Ludwig von Bertalanffy. The terms were later popularized by Dr. Timothy Leary in 1961 and have since become widely accepted by researchers in psychedelic therapy. This article explores the crucial role of set and setting in ensuring a safe, meaningful, and transformative psychedelic journey.