John Steinbeck's classic novel "Of Mice and Men" revolves around three thematic meanings: the elusive nature of the American dream, the idealized friendships between men and the cruelly dispassionate nature of life. The tale of George and Lennie shows the best and worst of human nature, and both of these men exhibit the depths and heights to which humanity can extend.
The ultimate cruelty of human life is an important theme in "Of Mice and Men." Just about all of the people in the book are profoundly lonely and isolated, and each of them wants a friend but will settle for talking to a stranger. Even when their isolation weakens them, many of them try to destroy those who are even weaker than themselves, as when Crooks focuses on Lennie's flaws or when Curley's wife threatens to get a lynching mob after Crooks.
One reason why the tragedy of George and Lennie's story runs so deeply is that it is clear they have lost a wonderful dream. They plan on living on a farm together, but that plan is not an easily attainable dream, especially for migrant workers. Even the sort of friendship they envision is not possible to sustain.