The Yen-Mullins model, also known as the modified Yen model, specifies the predominant molecular and colloidal structure of asphaltenes in crude oils and laboratory solvents and consists of the following: The most probable asphaltene molecular weight is similar to 750 g/mol, with the island molecular architecture dominant. At sufficient concentration, asphaltene molecules form nanoaggregates with an aggregation number less than 10. At higher concentrations, nanoaggregates form clusters again with small aggregation numbers. The Yen-Mullins model is consistent with numerous molecular and colloidal studies employing a broad array of methodologies. Moreover, the Yen-Mullins model provides a foundation for the development of the first asphaltene equation of state for predicting asphaltene gradients in oil reservoirs, the Flory-Huggins-Zuo equation of state (FHZ EoS). In turn, the FHZ EoS has proven applicability in oil reservoirs containing condensates, black oils, and heavy oils. While the development of the Yen-Mullins model was founded on a very large number of studies, it nevertheless remains essential to validate consistency of this model with important new data streams in asphaltene science. In this paper, we review recent advances in asphaltene science that address all critical aspects of the Yen-Mullins model, especially molecular architecture and characteristics of asphaltene nanoaggregates and clusters. Important new studies are shown to be consistent with the Yen-Mullins model. Wide ranging studies with direct interrogation of the Yen-Mullins model include detailed molecular decomposition analyses, optical measurements coupled with molecular orbital calculations, nuclear magnetic resonance (NMR) spectroscopy, centrifugation, direct-current (DC) conductivity, interfacial studies, small-angle neutron scattering (SANS), and small-angle X-ray scattering (SAXS), as well as oilfield studies. In all cases, the Yen-Mullins model is proven to be at least consistent if not valid. In addition, several studies previously viewed as potentially inconsistent with the Yen-Mullins model are now largely resolved. Moreover, oilfield studies using the Yen-Mullins model in the FHZ EoS are greatly improving the understanding of many reservoir concerns, such as reservoir connectivity, heavy oil gradients, tar mat formation, and disequilibrium. The simple yet powerful advances codified in the Yen-Mullins model especially with the FHZ EoS provide a framework for future studies in asphaltene science, petroleum science, and reservoir studies.