Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, is a motor neuron disease. In ALS, upper and lower motor neurons in the brain and spinal cord progressively degenerate during the course of the disease, leading to the loss of the voluntary movement of the arms and legs. Since its first description in 1869 by a French neurologist Jean-Martin Charcot, the scientific discoveries on ALS have increased our understanding of ALS genetics, pathology and mechanisms and provided novel therapeutic strategies. The goal of this review article is to provide a comprehensive summary of the recent findings on ALS mechanisms and related therapeutic strategies to the scientific audience. Several highlighted ALS research topics discussed in this article include the 2023 FDA approved drug for SOD1 ALS, the updated C9orf72 GGGGCC repeat-expansion-related mechanisms and therapeutic targets, TDP-43-mediated cryptic splicing and disease markers and diagnostic and therapeutic options offered by these recent discoveries.