This chapter explores the essential methodologies and considerations for histological analysis in the study of neurodegenerative diseases. It covers approaches to brain fixation techniques, sectioning strategies, and the selection of staining methods to accurately visualize neuronal, glial, and vascular changes. Emphasis is placed on aligning staining techniques with research goals and utilizing quantitative approaches such as stereology and image analysis for robust data interpretation. The importance of pilot studies and standardization in ensuring reproducibility is highlighted. A detailed description of key pathological changes, including neuronal degeneration, glial reactivity, vascular remodeling, and peripheral nerve changes, is also provided here to help readers focus on the dynamics and progression of histological changes in their experiments. By addressing these critical aspects, the chapter underscores the indispensable role of histological studies in advancing our understanding of nervous tissue pathology and developing targeted therapeutic interventions for neurodegenerative diseases.