Steinbeck turns the conventional buddy system on its ear by having one of the two good friends, Lennie, be mentally impaired.  Despite his disability, George, the more "with it" of the two friends, protects Lennie despite the costs to his livelihood and his status among his peers. 

The story is a fable of good vs. evil, of friendship vs. expolitation.  One of the primary characters, Curley's wife (never given a name) struggles with issues of dependancy and identity, a factor that is prevalent in all of the social situations of the novel, whether the relationship is between George and Lennie, Candy vs. Slim, or the "real" world vs. the idealized world to which George and Lennie aspire.

Steinbeck also examines the social system that puts characters who are uneducated and down-on-their luck against a system which seems to be designed to keep them down.  All in all, Of Mice and Men is an examination of the social constructs that existed in the early twentieth century and in some ways, still exists today.