From the outset, Kennedy makes it clear that his book aims to showcase instances of political bravery. He delves into the history of the U.S. Senate, highlighting past senators known for their integrity. The opening line of chapter one reads, "This is a book about the most admirable of human virtues—courage." Later in the chapter, he emphasizes that the tales he shares in Profiles in Courage are worth remembering, as are:

The accounts of other courageous senators—individuals whose unwavering dedication to their nation surpassed all personal and political agendas, who exemplified true courage and genuine faith in democracy. These were men who elevated the Senate of the United States beyond a mere assembly of individuals mechanically echoing the opinions of their constituents or a group of opportunists adept only at gauging and following public opinion trends.

Kennedy fulfills his commitment to illustrate the essence of political courage through historical examples. He recounts how John Quincy Adams, despite grappling with feelings of inadequacy, found the strength to oppose his party and constituents by supporting an embargo detrimental to his home state of Massachusetts. Kennedy explains that Adams did this because his vision was for a more robust America, not just a more powerful Massachusetts. In the case of Sam Houston, Kennedy depicts a man prioritizing the Union above all else, even though he hailed from a slave-holding state whose people advocated for secession. Through the story of Edmund G. Ross, readers discover a relatively unknown figure who, under immense political pressure, cast the pivotal vote against President Johnson's conviction. In each instance, the senator relinquished his political aspirations in a singular courageous act that embodied his principles.

In the opening chapter, Kennedy outlines three types of pressures faced by public officials. The first is the pressure to be liked, a universal human desire. Kennedy notes that for a senator, gaining approval often involves the ability to compromise. He argues that compromise is not indicative of weak morals or a lack of courage, but rather a wise understanding that achieving anything often requires negotiation. The second pressure is the pursuit of re-election. Senators aim to build long-lasting careers to have multiple chances to implement change, support what they believe is right, and oppose what they see as wrong. To achieve this, they must constantly focus on upcoming elections. Kennedy explains that in politics, individuals are expected to make significant personal sacrifices for the public good, and by showing their dedication to this, they improve their re-election prospects. The third pressure comes from constituents, special interest groups, and other organized entities that the senator represents. Kennedy writes that even if these groups form only a small part of the senator’s constituency, they cannot be disregarded or undervalued.

As Kennedy narrates the stories of various senators and congressmen, he subtly reminds readers of the pressures these public figures face. For instance, in the case of John Quincy Adams, all three pressures are distinctly illustrated. Kennedy notes that Adams was principled but not particularly likable. Adams consciously chooses to ignore the pressure of re-election when he adopts stances that clash with the views of his party and the people of Massachusetts. Lacking party support and the approval of his constituents, he recognizes his slim chances of re-election, yet he makes decisions based on his own conscience. The third pressure is evident when Adams starts receiving hostile letters from party members at home. He understands that he has distanced himself from his constituents' expectations, but he feels he has no alternative.

Kennedy stresses that these three sources of pressure cannot be overlooked. He adds that it is incredibly challenging for a politician to determine when to risk defying one of these pressures to uphold a value or principle. Such decisions are central to Profiles in Courage.