In this issue of the Journal, we publish 4 review articles (1–4) on gene-environment interaction (G×E) analysis in epidemiologic research. The papers resulted from a 2014 workshop held by the National Institute of Environmental Health Sciences and the National Cancer Institute to explore new approaches for discovery and characterization of G×E in epidemiologic research. The 4 papers provide an update on: 1) the state of the science in analytical methods of G×E (1); 2) opportunities for incorporation of biological knowledge into G×E analyses (2); 3) lessons learned from past G×E successes (3); and 4) overarching themes on current challenges and opportunities for gene-environment interaction studies of complex diseases (4). Topics include improved data analytical methods, environmental exposure assessment (5), and incorporation of functional information.