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A scientific (or empirical) skeptic is one who questions the reliability of certain kinds of claims by subjecting them to a systematic investigation. The scientific method details the specific process by which this investigation of reality is conducted. Considering the rigor of the scientific method, science itself may simply be thought of as an organized form of skepticism. This does not mean that the scientific skeptic is necessarily a scientist who conducts live experiments (though this may be the case), but that the skeptic generally accepts claims that are in his/her view likely to be true based on testable hypotheses and critical thinking.

Common topics that scientifically-skeptical literature questions include health claims surrounding certain foods, procedures, and medicines, such as homeopathy, Reiki, Thought Field Therapy (TFT), vertebral subluxations; the plausibility of supernatural entities (such as ghosts, poltergeists, angels, and gods); as well as the existence of ESP/telekinesis, psychic powers, and telepathy (and thus the credibility of parapsychology); topics in cryptozoology, Bigfoot, the Loch Ness monster, Global Warming, alien visitations, UFOs, crop circles, astrology, repressed memories, creationism, dowsing, conspiracy theories, and other claims the skeptic sees as unlikely to be true on scientific grounds.

Most empirical or scientific skeptics do not profess philosophical skepticism. Whereas a philosophical skeptic may deny the very existence of knowledge, an empirical skeptic merely seeks likely proof before accepting that knowledge.

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