Murine models serve as valuable tools for both comprehending the etiopathogenesis of diseases and for preclinical drug development. However, tackling neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) poses a significant challenge due to the described heterogeneity in patients and the multitude of pathogenic events involved. It is crucial to have a detailed understanding of the ALS models available and the defining elements of each to make an informed choice aligning with the objectives of each study. Thus, the first part of this article reviews the most widely used models generated for each of the main genes (SOD-1, TARDBP, FUS, and C9ORF72) involved in ALS. The second part compiles some techniques used to assess the effects of either drug treatments or genetic manipulations on disease progression. Techniques include compartmental, histological, and immunohistochemical analysis.