The quote reflects the unpredictability of life and death, emphasizing that no one, regardless of their wisdom or status, can truly understand the reasons behind these events. In "Lonesome Dove," characters face the harsh realities of existence, where fate does not discriminate based on intelligence or bravery. This sense of randomness underscores the fragility of life and challenges the notion that certain qualities guarantee survival.

The observation that wise men can perish before fools, and cowards before the brave, further illustrates the theme of survival as an inexplicable phenomenon. It highlights the inherent mystery surrounding mortality, suggesting that there is no clear logic or fairness in who lives and who dies. Ultimately, McMurtry presents a sobering truth about the human experience, inviting readers to ponder the randomness of life.