Models derived from X-ray crystallography can give the impression that proteins are rigid structures with little mobility. NMR ensembles may suggest a more dynamic picture, but even these represent a rather narrow range of possibilities close to the lowest energy state. In reality proteins participate in a wide range of dynamics from the subtle and rapid sidechain dynamics that occur in nanoseconds in the PDZ signaling domain to the large and slow rearrangement of secondary structure that takes days in the mitotic checkpoint protein Mad2. Between these extremes are motions on time scales typically associated with protein function, such as those in SNase monitored by hydrogen exchange. The dynamic character of several protein systems, including PDZ domain, Calmodulin, SNase, and Mad2, were explored using a variety of biophysical techniques. This broad investigation demonstrates the dynamic variability between and within proteins. The study of PDZ and Calmodulin illustrates how a computational technique can recapitulate experimental results and provide additional insight into signal transduction. The case of SNase shows that HX NMR data can be exploited to reveal protein dynamics with unprecedented detail. The Mad2 system highlighted some of the pitfalls associated with this technique and some alternative strategies for investigating protein dynamics.