We examined characteristics of routinely cataloged seismicity from 1970 to the present in and around the Yakima fold-and-thrust belt (YFTB) in eastern Washington to determine if the characteristics of contemporary seismicity provide clues about regional-scale active tectonics or about more localized, near-surface processes. We employed new structural and hydrologic models of the Columbia River basalts (CRB) and found that one-third to one-half of the cataloged earthquakes occur within the CRB and that these CRB earthquakes exhibit significantly more clustered, and swarmlike, behavior than those outside. These results and inferences from published studies led us to hypothesize that clustered seismicity is likely associated with hydrologic changes in the CRB, which hosts the regional aquifer system. While some general features of the regional groundwater system support this hypothesis, seismicity patterns and mapped long-term changes in groundwater levels and present-day irrigation neither support nor refute it. Regional tectonic processes and crustal-scale structures likely influence the distribution of earthquakes both outside and within the CRB as well. We based this inference on qualitatively assessed alignments between the dominant northwest trends in the geologic structure and the seismicity generally and between specific faults and characteristics of the 2009 Wooded Island swarm and aseismic slip, which is the only cluster studied in detail and the most vigorous since regional monitoring began.