<p>Understanding electron transport has long been a central challenge in condensed matter physics and materials science, owing to the complexity of electronic band structures and the diverse mechanisms by which electrons interact. Early approaches often relied on simplified models or empirical parameters, limiting both their accuracy and predictive capabilities. Recent advances in first-principles calculations have enabled rigorous quantification of band structures and scattering processes without empirical parameters, which makes it possible to directly compute electronic transport properties — such as mobility and conductivity — with unprecedented details and even predict novel materials. In this Review, we illustrate material cases in which first-principles approaches have provided detailed and quantitative insights into the electron transport mechanisms and highlight the emergent chemical intuition that rationalizes these transport properties. We discuss how these insights have guided the discovery of new materials, including high-mobility semiconductors and thermoelectric compounds, and the potential to expand these first-principles techniques to a broader class of materials and structures.</p>