The title refers to a character in Lewis Carroll's "Through the Looking-Glass" who tells Alice that in her world, "it takes all the running you can do, to keep in the same place." This serves as a metaphor for evolutionary biology where species must constantly evolve (run) just to maintain their fitness relative to competing species or parasites that are also evolving. In the context of sexual reproduction, Ridley argues that we must constantly create new genetic combinations through sex just to stay even in the evolutionary race against parasites and pathogens.

The book presents evidence that men and women have evolved different reproductive strategies based on asymmetries in parental investment, leading to statistical differences in psychology and behavior. However, Ridley is careful to distinguish between evolved predispositions and determinism. He acknowledges significant overlap between male and female traits and behaviors, and emphasizes that evolutionary explanations don't justify sexism or inequality. Rather, understanding these differences can help explain certain patterns in human mating behavior while recognizing the enormous role of individual variation, culture, and personal choice.

Ridley describes humans as having a "system of monogamy plagued by adultery," suggesting our mating system reflects competing evolutionary pressures. He examines evidence that humans evolved with both pair-bonding tendencies and inclinations toward extra-pair mating, depending on circumstances. The book explores how this tension between monogamous commitment and attraction to others manifests in human societies, relationships, and moral systems. Rather than presenting a simplistic view that humans are "naturally" monogamous or polygamous, Ridley shows how our complex mating psychology reflects adaptive solutions to reproductive challenges faced by our ancestors.