Lactating dairy cows are classified as spontaneous ovulators, in which establishment of pregnancy depends on the accuracy of detection of behavioral estrus for correct timing of artificial insemination (AI). Development of the Ovsynch protocol, a hormonal protocol that synchronizes ovarian function, thereby allowing for timed AI (TAI) without the need to detect estrus, provided a management tool for increasing AI service rates but not pregnancies per AI (P/AI). A review of 7 randomized, controlled experiments that compared P/AI of cows inseminated after a detected estrus to that of cows receiving TAI after submission to Presynch-Ovsynch or Double-Ovsynch protocols supports that the newest programs for TAI yield more P/AI than cows inseminated after a detected estrus. The physiologic and endocrine mechanisms that explain how fertility programs increase P/AI are a culmination of over 20 yr of research aimed at increasing reproductive performance in lactating dairy cows. We illustrate the dramatic change in reproductive performance of US dairy cows over time by comparing the phenotypic trend in days open with the genetic trend in daughter pregnancy rate and the phenotypic trend in cow conception rate. Whereas days open increased from 1955 to 2000, days open from 2000 to 2010 dramatically decreased without a concurrent increase in the genetic trend for daughter pregnancy rate. By contrast, the dramatic decrease in days open over the past 20 yr is associated with a dramatic increase in the phenotypic trend in cow conception rate. Although many management factors affect P/AI, adoption and implementation of TAI programs that directly increase P/AI is an important component of the dramatic increase in reproductive performance in lactating dairy cows in the United States over the past 20 yr.