Amyotrophic lateral sclerosis (ALS) is a common late-onset neurodegenerative disorder that affects motor neurons. There is no conclusive etiology of ALS, though approximately 2% of cases have been linked with mutant Cu, Zn-superoxide dismutase (SOD1). A plethora of mechanisms that contribute to ALS disease progression have been discovered in the last two decades, including nonneuronal cell signaling, activation of the apoptotic cascade, and excitotoxicity. Though conclusive diagnosis of ALS remains elusive and though there is still no known effective treatment for this disease, continuously exploring the pathology would provide insight into the creation of novel technologies for the treatment and diagnosis of ALS. In this review, we provide an overview of hypothesized mechanisms and possible biomarkers for ALS pathology, in the first section. In the following section, we introduce recent nano/biotechnological approaches in studying disease mechanism and developing diagno-therapeutic methods for ALS.