The basic premise of this "absurd" play is that two men are waiting for another, who never comes. Its theme centers around the futility and emptiness of life. Man struggles to find meaning in life, but our place in the world is insecure. The only thing that might have meaning for us is the quest to find that meaning. And, IF God is there, he created us, threw us into existence, and left us to shift for ourselves. He doesn't care about us. It is a very existential view of life.
Samuel Becket was one of many authors to have lived through the destruction of World War II and the ensuing uneasy Cold War period of the 1950s and 1960s. Seeing how man nearly wiped himself out with modern warfare caused many writers to examine the nature of the human condition. In spite of this, however, the play does focus on a meaningful friendship between Estragon and Vladimir, so the concept of friendship and human relationships as being a way of coping and struggling with existence in a meaningless world is also a theme of the work.
Read about the themes here on enotes.