This 45-letter behemoth was coined in 1935 by the president of the National Puzzlers' League of the United States, Everett E. Smith, in a presentation about the ever-growing length of medical terms. When he used the word, no one in the audience, which included a number of doctors, even recognized the term. Why?
Because he had made it up.
Smith coined it to show how ridiculously long medical terms had gained acceptance. But he didn't pull it out of thin air. It was created by stringing together a series of Latin stems that, taken together, could conceivably describe an inflammatory lung disease caused by the inhalation of fine silica dust, a real disease already known popularly as black lung and technically called pneumoconiosis or silicosis.
Although some people call pneumonoultramicroscopicsilicovolcanoconiosis the longest word in the English language, others cry foul because the word was coined precisely to be an extremely long word. Somehow, though, it managed to appear in a dictionary in the late 1930s — possibly because of an organized effort by members of the NPL — and so found its place in language history.
The longest word in the English language that wasn't coined for the purpose of being long is antidisestablishmentarianism, which refers to the opposition of the disestablishment of the Church of England (though it wouldn't seem impossible for the even-longer antidisestablishmentarianistically to have found its way naturally into the language).
At 28 letters, antidisestablishmentarianism just beats out the 27-letter honorificabilitudinitatibus — able to achieve honors — which is the longest word in Shakespeare's works (Love's Labour's Lost, Act V, Scene 1) and also appears in James Joyce's Ulysses. This word is also notable because it is made up entirely of alternating consonants and vowels.