In the United States, joint diseases affect more than 50 million people, a number that is expected to rise in the next few decades. Hallmarks of joint disease often involve degradation of articular cartilage tissue, which leads to patient disability and pain. Articular cartilage cannot heal very effectively on its own, and there is a limited understanding on which therapeutics would be most effective in disease treatment. Because of the inherent complexities of cartilage, it is often difficult to predict how therapeutics will be transported through the tissue, especially for larger molecules. For proper development of effective therapeutic strategies, a better understanding of transport of larger therapeutics is needed. First, a review of molecular transport in cartilage is presented to better motivate this work (Chapter 1). There are many molecular and environmental factors that affect transport for larger solutes, such as hydrodynamic size and/or molecular weight (Chapter 2), charge (Chapter 3), and the presence of fluid flow within the tissue (convective transport) (Chapter 2 – 4). Additionally, the heterogeneities in composition within the tissue is important and can be used to predict cartilage transport (Chapter 5). Finally, this new macromolecular data informed the development of a predictive framework under which transport of solutes over a wide range of sizes can be accurately predicted (Chapter 6).