Leaving one mating relationship and entering another, serial mating, is commonly observed in many cultures. An array of circumstances can prompt a mate switch. These include (1) unanticipated costs inflicted by one's mate, or ‘relationship load,’ not apparent on the initial mate selection; (2) changes in the mate value of either partner, creating discrepancies where none previously existed; and (3) the arrival of a new and interested potential mate of sufficiently incremental value to offset the costs of a breakup. The mate switching hypothesis suggests that these circumstances created adaptive problems throughout human evolution that forged adaptations to anticipate and appraise opportunities to mate-switch, implement exit strategies, and manage challenges confronted in the aftermath. We review several studies that support various aspects of the mate switching hypothesis: The cultivation of ‘back-up mates,’ assessing mate-inflicted costs that comprise relationship load, monitoring selfishly-skewed welfare tradeoff ratios in a partner, gauging mate value discrepancies, and anticipating sexual, emotional, and economic infidelities. The mate switching hypothesis provides both a complementary, and in some instances a competing, explanation to the ‘good genes’ hypothesis for why women have sexual affairs, and parsimoniously explains a host of other mating phenomena that remain inexplicable on alternative accounts.