For the past several years, a large group of collaborators has been working together toward understanding key biological problems related to brain function, brain structure, and the complexity of the nervous system. Problems such as the structure and the function of pre-and post-synaptic densities, the sets of proteins that are regulated by mental processes such as learning and memory formation, the protein networks affected by apoE genotypes in Alzheimer’s disease patients, and the structure of synaptic protein complexes in animal models of epilepsy, just to mention a few, have been under scrutiny in these studies. To tackle biological problems using neuroproteomics, we have learned that multiple experimental approaches need to be implemented. Techniques such as 2D-DIGE, mass spectrometry (MS), MS-based tissue imaging, protein arrays, surface plasmon resonance (SPR), protein interaction network analysis, multidimensional liquid chromatography, and many others are now in daily use. This book is intended to provide the reader with an introduction to some of the techniques that are most commonly used in neuroproteomics, and includes some examples of how such techniques are used to understand biological processes. A general overview of these techniques and their scope is discussed in this chapter.