Variability of sea-surface temperature related to shifts in the mode of the El Nino-Southern Oscillation (ENSO) has been implicated as a possible forcing mechanism for the global-scale changes in tropical and subtropical precipitation known as the 4.2 ka event. We review records of coral reef development and paleoceanography from the tropical eastern Pacific (TEP) to evaluate the potential impact of the 4.2 ka event on coral reefs. Our goal is to identify the regional climatic and oceanographic drivers of a 2500-year shutdown of vertical reef accretion in the TEP after 4.2 ka. The 2500-year hiatus represents similar to 40% of the Holocene history of reefs in the TEP and appears to have been tied to increased variability of ENSO. When ENSO variability abated approximately 1.7-1.6 ka, coral populations recovered and vertical accretion of reef framework resumed apace. There is some evidence that the 4.2 ka event suppressed coral growth and reef accretion elsewhere in the Pacific Ocean as well. Although the ultimate causality behind the global 4.2 ka event remains elusive, correlations between shifts in ENSO variability and the impacts of the 4.2 ka event suggest that ENSO could have played a role in climatic changes at that time, at least in the tropical and subtropical Pacific. We outline a framework for testing hypotheses of where and under what conditions ENSO may be expected to have impacted coral reef environments around 4.2 ka. Although most studies of the 4.2 ka event have focused on terrestrial environments, we suggest that understanding the event in marine systems may prove to be the key to deciphering its ultimate cause.