Gas hydrates are ice-like solids that can readily form and restrict flow in high-pressure natural gas transmission lines. The use of antifreeze thermodynamic inhibitors dominated production systems throughout the 20th century, where most research necessarily focused on measuring and predicting the hydrate phase boundary. In the 21st century, market competitiveness and environmental constraints have motivated a paradigm shift toward the identification and management of hydrate blockage risks, which has largely been facilitated to date through two research efforts: establishing and continuously refining mechanistic models to predict hydrate blockage formation; and exploiting critical stages within that blockage mechanism to develop novel, environmentally compatible inhibitors. This review presents a historical perspective on the development of an oil-dominant blockage mechanism and the technologies enabled by these efforts. Efforts over the past decade - made possible through the collaboration between industry, the Australian government, and academia - are then summarized in the context of producing the first mechanistic blockage model for gas-dominant transmission lines, including the role of innovative high-pressure pilot-scale flowloop systems. Together, these blockage mechanisms have enabled new opportunities to develop and deploy low-dosage hydrate inhibitors - including the creation of new experimental capabilities that can be used to quantify occurrence probability or severity and the transient simulation tools that can leverage such knowledge - that support the ability to quantitatively manage hydrate blockage risk in hydrocarbon transmission lines. As they offer superior resolution in performance assessment to first-generation approaches, these new experimental methods offer structure-function design and optimization of low-dosage inhibitors against secondary, environmental parameters.