The title of this episode is a reference to the Great Chicago Fire of 1871. When it happened, the fire was blamed on a cow belonging to a Mrs. O'Leary that allegedly kicked over an oil-burning lamp in a barn, setting fire to the hay.
The GPS coordinates are Latitude 33.12003 and Longitude 112.31893. (The writers flipped these coordinates, perhaps in an effort to prevent showing a real location.)
Chad Lowe who guest-stars in this episode would again work with series regular Sofia Vassilieva in the TV series Supergirl (2015).