The potential existence or non-existence of psychic abilities, also known as psi, has been investigated scientifically for about 150 years (since 1858), according to the US National Academy of Sciences. In 1985, the organization released a statement that concluded there is "no scientific justification from research conducted over a period of 130 years for the existence of parapsychological phenomena." According to a survey, just 2% of scientists in the National Academy of Sciences believed in psi phenomena or psychic abilities.

According to parapsychologists, these scientists are being closed-minded, and some psi phenomena including ESP (extra-sensory perception) and psychokinesis have experimental support. Most scientists argue that any apparent experimental support for the existence of psychic abilities is either within the margin of what would be predicted by chance (this accusation is especially frequent when the sample size is low), constitutes deliberate fakery (either by the experimenters or the subjects), or is due to a poor experimental design that subtly biases results towards affirmation of the existence of psi.

A 2008 study by Kosslyn and Multon based on neuroimaging tested for several psychic abilities including clairvoyance, remote viewing, and precognition, and found no distinguishable neural responses when a "receiver" viewed an image being psychically sent by a "sender" versus a random image. This effect persisted even when conditions alleged to magnify psychic abilities were used, such as the use of twins, siblings, or spouses. The scientists called these experiments "the strongest evidence yet obtained against the existence of paranormal mental phenomena."

One of the early and most popular tests for the presence of psi phenomena are the famous Zener cards, five cards with symbols on them: a circle, a cross, wavy lines, a square, and a star. The experimenter goes through the deck of cards, observes the result, and (while concealing the card) asks the subject to name the symbol on the other side. After many thousands of these experiments, participants rarely performed better than chance, and when new experimental controls were introduced, such as shuffling the cards using a machine, conducting a larger number of trials, and separating the participant and experimenter by a larger distance, the effect all but disappeared. Karl Zenner demonstrated a poor understanding of statistics and the scientific method, for instance interpreting worse-than-chance results as indicating the presence of psi phenomena ("psi-missing") and attributing convergence to chance performance over time (which is to be expected if psi isn't real) as due to boredom with performing the tests in the first place.

Since a brief resurgence of activity in the 1970s, nearly all university departments practicing psi research have been shut down. Today, only two remain, the University of Virginia's Department of Psychiatric Medicine, and the University of New Mexico's Veritas Laboratory.