This was the first note issued in the Frontiers series. The  theme is innovation in medical research, and the vignette on the back is anchored by the image of a researcher looking into a microscope. The scientist represents medical research in Canada and the nation’s commitment to it. She is surrounded by images of a DNA strand and the readout of a healthy heartbeat from an electrocardiogram monitor. The illustration of the insulin bottle celebrates the discovery of insulin by Canadian research scientists Frederick Banting and Charles Best. The image is a faithful reproduction of an actual example of one of the earliest insulin bottles, dated 1923.

The large window on the note features a smaller, colourized version of the portrait of Sir Robert Borden with an image of the tower from the East Block of Parliament, both in colour-shifting foil.

The note was released on 14 November 2011 (World Diabetes Day), at the MaRS Discovery District in Toronto, near the site of the Banting and Best laboratory. The $100 note was nominated for Bank Note of the Year for 2011 by the International Bank Note Society.