Amyotrophic lateral sclerosis (ALS) is an adult-onset, incurable neurodegenerative disease characterized by the selective death of upper and lowers motor neurons in the spinal cord, brainstem and motor cortex, which ultimately leads to paralysis and death within 2-3 years of onset. ALS is poorly understood, although multiple studies have been proposed to explain the pathophysiological mechanisms of the disorder. The development of microarray technology, for simultaneous analysis of the transcriptional expression of thousands of genes, has provided new possibilities to get better insights into the pathogenesis of ALS, and most important, potential new candidate targets for novel treatments. The present review illustrates current evidences from transcriptomic studies in animal models and human samples, related to ALS pathogenesis in parallel to molecular targets associated with the disease progression. Additionally, alteration of RNA metabolism was identified as a major dysregulated pathway in ALS and via this study, new insights into the contribution of altered transcriptional profiles of microRNAs and ALS-associated ribosomal binding proteins have been investigated, in an effort to understand the functional consequences of widespread RNA dysregulation in the disease's pathological mechanism.