The development of vital fluorescent synthetic dyes and the generation of a myriad of genetically encoded fluorescent proteins permit sensitive visualization of a broad range of dynamic features in living cells with fluorescence microscopy. Many neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Creutzfeld-Jacob disease (CJD), Huntington's disease (HD), multiple sclerosis (MS), and Parkinson's disease (PD) share common aspects on a cellular level that are associated with a change in the dynamic behavior of the whole cell, cell compartments, or single proteins. These include disturbances of transport mechanisms or protein turnover, missorting and aggregation of proteins, and changes in the structural plasticity of neurons. In this chapter, we describe different live-cell-imaging techniques, present representative examples, and discuss the current and potentially future use of live-cell-imaging approaches to answer key questions regarding the mechanisms or potential treatments of neurodegenerative diseases.