We discuss how we combine multiple biophysical and single molecule approaches to following the aggregation of proteins. Using a global approach to fitting our data, we model aggregation behavior using aggregation free energy landscapes. From these landscapes we develop a language for understanding the role of different type of oligomers in the aggregation mechanism. We will highlight two systems: ß-lactoglobulin and α-synuclein. Both of these proteins can convert from a disordered state into amyloid fibrils. In the case of α-synuclein, it appears that a hydrophobic interface is required to overcome the large barrier to aggregation. We will discuss the free energy landscapes that arise from our combination of experiments and mechanistic modeling. We will show data that suggests that the there is a conformational change occurring at the interface that depends on the chemical and physical nature of the interface. We propose that the conformational change is what promotes the aggregation of α-synuclein into fibrils.