If we understand this play to be about existential despair, then this repeated line makes perfect sense as an illustration of the play's theme. Existentialism arose most vigorously after World War II (notably, the play was written in 1948) to express the senselessness of a world that seemed without purpose and without God as Europeans in particular coped with what seemed like senseless destruction and carnage. In this play, the phrase "nothing to be done" expresses the hopelessness of action—and the senseless ways action sometimes succeeds. It is the first line of the play; Estragon uses this expression, which we tend to interpret as very grand and universal, about a banal action that, as Vladimir says, is done every day: taking off a boot. Despite the simplicity of the act, at first Estragon fails. Later in Act I, Vladimir says "nothing to be done" as Estragon continues struggling to get his boot off. Rather than helping Estragon, he is musing about hope deferred and says the line right before Estragon does finally get his boot off. This points to the absurdity of utterance, for just as Vladimir makes this hopeless statement, Estragon succeeds with the boot. The phrase shows up again as Vladimir and Estragon discuss Jesus and then that "the essential doesn't change." In Act II, as they are waiting for Godot, Vladimir says a variant of the this: "There's nothing we can do." We can do nothing, except perhaps wait, because we are all trapped in a universe that doesn't make sense.
It is one of those lines that are repeated throughout the play. Beckett builds his drama on a subtly repetitive structure of intra-textual referentiality. 'Nothing to be done', is not only the opening line of the play as spoken by Vladimir but it recurs through the play and is repeated by Estragon later. It is used to strengthen the bond between Didi and Gogo, the 'pseudocouple' on the level of speech-event and indicates their unitary figuration in the play.
The point to note is the passive grammatical construction of the line that connects with its thematic and philosophical stress on Man's passivity in a world of divine absence. God, as in Christian terms, is the sole active agent in an otherwise passive world and in his absence, there is very little to do apart from passing the time with the insignificant actions e.g. the hat-routines of Didi nad Gogo, their sterile, unfinished acts of storytelling, discourse in general and so on. 'No-thing' philosophically connects with the Sartrean notion of 'non-being' as well as beckett's own idea taken from Greek antiquity--"Nothing is more real than nothing". It also implies an exhaustion of the logical and ego-enabling process of meaning-making in life. As Deleuze famously said, Beckett's characters 'exhaust the combinatorial'. Vladimir's opening line is located at the dead-end of his life-long rationalist quest for signification. Vlkadimir, as Deleuze would say, cannot even 'possibilitate'. The triviality of human action, as expressed in the line also couples with a self-fantasized waiting for a significance of life, that is never to arrive.
The opening line of Waiting for Godot is: ‘Nothing to be done.’ Spoken by Estragon when he fails to remove his boot. And the line is repeated at intervals during the play and could be said to be one of the main ideas behind the script. Beckett keeps everything wonderfully simple, and this metaphor, that sometimes you can’t get your boots off and sometimes you can, and there is no way of knowing why or when and Nothing to be done about it, tolls away in the recesses of consciousness while the players are on stage.
In my english drama class my teacher who majored in Beckett also mentioned how "Nothing to be done" refers to the play, theater, and life.