Holotropic Breathwork was developed by Stanislov and Cristina Grof during the 1970s and 1980s. But the early stages of its development occured in the late 1960s in Czeckoslovakia. Stanislov Grof, M.D. studied medicine and psychoanalysis at the Charles University School of Medicine in Prague in the early 1950s. In the 1960s, Dr. Grof became a principle investigator in a clinical study of the possible therapeutic potential of a psychedelic drug provided by Sandoz Pharmaceuticals. He noticed that under highly controlled conditions, many subjects entered a "nonordinary state" which was "indistinguishable from those described in the ancient mystical traditions and spiritual philosophies of the East."

In 1967, Dr. Grof came to the United States to continue his research He became an Assistant Professor at Johns Hopkins University and the Chief of Psychiatric Research at the Maryland Psychiatric Research Center in Baltimore, Maryland. Out of his friendships with the founders of humanistic psychology, Abraham Maslow and Anthony Sutich, they started a new discipline called "Transpersonal Psychology." This form of psychology addresses experiences which are outside the boundaries of our body and personal identity.

During this time, Dr. Grof began to develop his map of human experiences in nonordinary states. This included sensory, biographical, perinatal, and transpersonal experiences. In addition, Dr. Grof developed the Basic Perinatal Matrices (BPMs) of the birth process (BPM1-BPM4) and the an theory on the association between traumas in experienced nonordinary states call Condensed Experiences (COEX).

In 1974, after ten years of yoga practice (including Hatha Yoga and Siddha Yoga/Kundalini Yoga), Christina Grof experienced what might be called a "Kunalini Awakening" (a sudden experience of life-force energy and change in consciousness) during a meditation period led by a Siddha Yoga Master from South India. This led to a roller coaster of emotional experiences over the next year. In 1975, Christina Grof was referred to Dr. Stan Grof who helped her by staying with the emotions and moving through them.

In the late 1970s, Stan & Christina Grof got together in California and began to develop Holotropic Breathwork. Dr. Grof knew from his scientific research that transformation can occur in nonordinary states of consciousness and that the most powerful technique of inducing nonordinary states was psychedelic substances. (Psychedelic plant substances have been used in many cultures to induce nonordinary states and transformation.) However, Dr. Grof also knew that such substances involve serious risks. Therefore, the Grofs developed a safe and effective way of using one's own breath to induce nonordinary states of consciousness.

In 1980, Christina Grof founded the Spiritual Emergence Network (SEN) to help the many individuals who, like her, are struggling or had become stuck with their own inner transformation.

In the early 1980s, Stan and Christina Grof travelled all over the world conducting workshops and giving lectures related to Holotropic Breathwork and Transpersonal Psychology. By 1987 they had developed their first structured training program. Between 1987 and 1994 the Grofs facilitated Holotropic Breathwork Sessions for more than 25,000 people.