I spotted this sign recently in a major NHS children’s hospital and I had to smile (perhaps that’s the point, though I reckon the humor is too nerdy for most kids — or their parents). It’s an example of colour contrast, first outlined by Johann Wolfgang von Goethe, and shows that some colour combinations just don’t work, in this case yellow and white.
So the joke is that the one statement that’s most difficult to read is all about communication.
Some colours just don’t work with each other, if your main aim is clear communication. Yellow on White (although white on a deep yellow may work); Green on Red; Red on Green; Blue on Blue; the list goes on an on …
Fortunately, there are several web-based tools to help you choose color schemes. My favorites are ColorJack which is very good for accessibility testing; DeGraeve’s Palette Generator; Colormixers; and the 4096 Color mixer.