devastated cities of World War II, he remarks, "There never could have been so many/Suffered more for less.’’ Throughout the play, Nickles taunts Zuss about the world's suffering and mocks humans like J.B. for believing that God cares about their pain. The masks worn by Nickles and Zuss symbolize their connection to human suffering: Zuss's God-mask has blind eyes, while Nickles's Satan-mask has open eyes. Nickles points out, ‘‘Those eyes see.’’ Ultimately, J.B. does not fall into despair, but Nickles does. Nickles comes to believe that J.B.'s best option is to end his own life, rejecting the world God has made. For many readers, this sense of hopelessness is the play's central theme. It is only in the final scene that the audience finds any reason to glimpse hope.

MacLeish frequently discussed and wrote about his play J.B., always making clear what he intended it to convey, even though, as the poet who famously wrote, "A poem should not mean / But be," he was somewhat hesitant to delve into themes. While speaking to the cast of a college production in 1976, he clarified, "The play is not a struggle between God and J.B." He explained that the play's core question is about "the justification of the universe's injustice."

This theme is reflected through the characters of J.B. and Sarah. Initially, J.B. believes he is prosperous and blessed because he has earned God's favor, interpreting his wealth as a form of justice. When his children are tragically taken from him one by one, he searches for reasons behind his suffering. Even though Nickles and Zuss (symbolizing Satan and God) agree that J.B. is innocent and does not deserve his fate, J.B. can only perceive his situation in terms of justice. Thus, he concludes that he and his children must have sinned. Conversely, Sarah dismisses the notion that justice is the root of their trials. In scene 8, she implores J.B. not to "betray" their children by labeling them sinners: "I will not / Let you sacrifice their deaths / To make injustice justice and God good!" When J.B. ignores her plea, she departs from him.

Sarah returns in scene 11, having come to the realization that the world and the love shared among people are sufficient reasons to continue living. She tells J.B., "You wanted justice, didn't you? / There isn't any. There's the world." She explains her departure by saying, "I loved you. / I couldn't help you any more. / You wanted justice and there was none—/ Only love."

When MacLeish brought J.B. to Broadway, he and director Elia Kazan decided that for the play to succeed on stage, J.B. should ultimately resolve the conflict between justice and love. As a result, in the acting edition, the final scene was revised to give J.B. most of Sarah's concluding lines, further expanding on them. In both versions, it's clear that God does not love humans nor does He act out of justice or injustice; He simply exists. It is humans who have the capacity for love. In a world where blessings and sufferings are neither earned nor deserved, people must choose to love one another or succumb to despair.

As a twentieth century Job, J.B. could have been depicted as a victim of his own success—some selfish or arrogant businessman who takes credit for his high standard of living. Archibald MacLeish chooses, however, to make him an unwilling but empathetic participant in his century’s meaningless suffering. MacLeish has explained that he saw in the biblical Job a vehicle for examining the “inexplicable sufferings” of humankind in the modern world—a world in which millions could be killed because of their race or simply because they were inhabitants of a certain city. J.B. is delivered into the hands of a God who mistrusts him more than Satan does, indeed, a God who is more satisfied with winning a bet than in proving the faithfulness of his disciple.

It can be said that J.B. asks questions similar to those asked by the biblical Job, but in a different religious context. J.B. lives in a postbiblical—specifically post-Christian—world; piety and fidelity are ornaments to be hung on already achieved success, not the means toward achieving it. In the midst of his grand achievements, J.B. would never have been prompted to ask: How can man love and serve a God who seems to be indifferent to (or unable to resolve) the issue of cosmic evil as it manifests itself on the earth? To ask this question, one must step into history and not cocoon oneself within the sanctity of home and family. The biblical Job finally accepts the answer that God’s justice and mercy escape mankind’s ability to understand it, and thus Job must simply accept what has happened to him as an exercise of Divine freedom that ultimately has restored Job’s losses. In contrast, the answers discovered in the course of J.B. are less orthodox and less theological.

One response to J.B.’s predicament in the play is foreshadowed by J.B.’s wife, Sarah. Early in the play, she is as likely to attribute their affluence to luck as to God’s grace. It is she who, in the end, returns to J.B. and announces that there is no justice in the world and, perhaps, no God to fear offending—or, at least, no God worth trying to offend. J.B., though he has defended the “system” of God’s justice throughout—wishing only he could see what his sin is—reluctantly concedes this point, proclaiming that the light they need to build a new life will come from within, not from without. J.B. is thus a product of the emerging humanist consensus and bears the marks of its earthbound theology: Without mankind’s love and obeisance, God is at best a creator; it is only in mankind’s ups and downs, mankind’s tragedies and victories, that God can be seen as superior and worthy of honor. In the climax of J.B., it is Satan—as he arguably does in John Milton’s Paradise Lost—who seems to emerge as the more sympathetic and compassionate character. The implication is that as soon as men and women discover this—as J.B. and Sarah do at the play’s end—they no longer need God; they have the opportunity to grapple with human suffering without slogans and empty religious dogma.