More than a half century after plate tectonics provided an overarching framework to explain earthquakes along active plate boundaries, numerous theories have been proposed to explain where, why, and how often earthquakes occur well away from active plate boundaries, but a paradigm remains elusive. Even the classification of earthquakes away from active plate boundaries as "intraplate" raises issues, with potentially important distinctions between Stable Continental Regions and more actively deforming regions including passive margins and failed rifts. Some of the largest known intraplate earthquakes themselves remain enigmatic, having occurred before the modern instrumental era. Hazard assessments are often data-limited: low fault-slip rates relative to landscape modification rates result in poor discoverability of fault sources, challenging the characterization of source zones and earthquake recurrence; the completeness and homogenization of instrumental earthquake catalogs using uncertain magnitude conversions can lead to uncertainties in earthquake recurrence; and, limited strong-motion observations for large-magnitude events at near-source distances leads to uncertainties in the selection and development of ground-motion models for seismic hazard studies. Data from recent intraplate earthquakes around the world—from the moment magnitude M 7.7 2001 Bhuj, India, earthquake 25 years ago to the 2024 M 4.8 Tewksbury, New Jersey earthquake—have yielded both new insights and new questions. The papers in this special focus discuss many of the long-standing challenges involved with intraplate earthquake investigations and provide a snapshot of the state of the art with current research to advance our understanding.