An old college acquaintance, Reginald Musgrave, asks Holmes to help him solve the mystery of his missing butler. Holmes's career is still in its earliest stages, and he is eager to take on the challenge. The most prominent clue is, in itself, a riddle - the "Musgrave Ritual" that has been passed down in the family for generations. Holmes believes if he can solve the riddle, all the rest of the mystery will fall into place.
This story gives a lot of great insights on Holmes himself - specifically, his methods. He is one who focuses on gaining and using practical knowledge that will help him in his work (we'll hear more about that in A Study in Scarlet!). Sometimes that practical knowledge may seem almost random. In this instance, he makes use of his knowledge of math, history, and human psychology to approach the problem.
There are two great adaptations of this story which I just want to mention. One is a TV episode, from the fantastic Sherlock Holmes series starring Jeremy Brett. It takes a few liberties with the story, but it overall it follows it closely. A small clip:
Another one I enjoy is the Basil Rathbone movie Sherlock Holmes Faces Death. The plotline combines the concept of a riddle with the game of chess, all in a spooky house (for added drama). Granted, it's more of an "inspired by" film than a purist adaptation, but it's great fun to watch.