Harlequin was started in Winnipeg, Manitoba in 1949. At first they published only reprints, but soon started publishing paperback originals, including Brian Moore's first two books. They published a wide variety of subject matter, including science fiction, mystery, western, historicals, cookbooks. etc.
In the late 1950's, they began the transition to the romance novel publisher we know them as today, when they acquired North American rights to the British Mills & Boon romance books. 1960 saw only a handful of non-romance title being published, and by 1963, they were publishing ONLY romances. In 1971, their success allowed them to purchase Mills & Boon.
Harlequin started their numbering with #1, and those collectors not into the romance titles generally consider the first 500 titles as the collectible ones, with a handful of titles higher than that number not being romance. For those who ARE into romance, #500 is a good starting point, with perhaps a few dozen romances published prior to that date.
Over the years, Harlequin has also experimented with other publishing lines, including Laser (science fiction), Raven House (mystery), Gold Eagle (adventure series), Worldwide Library (mystery), etc.