Being the fifth book in a trilogy it wasn't clear that this was the concluding book in the series until Douglas Adams's death on May 11, 2001.
The title comes from a joke early in the series, when Arthur Dent discovers that the entry for Earth in The Hitchhiker's Guide to the Galaxy consists, in its entirety, of the single word "Harmless". His friend Ford Prefect, a contributor to the Guide, assures him that the next edition will contain the article on Earth Ford has spent the last few years researching—somewhat cut due to space restrictions, but still an improvement. The revised article, it transpires, will read "Mostly harmless."