Pain is a largely neglected symptom in patients with amyotrophic lateral sclerosis (ALS) although it is reported by most of these patients. It occurs at all stages of the disease and can be an onset symptom preceding motor dysfunction. Pain is correlated with a deterioration in patients’ quality of life and increased prevalence of depression. In the later stages of ALS, pain can be severe enough to require increased use of sedative and analgesic drugs, and is among the events that predict clinical deterioration and death. The site of pain depends on the pain type or underlying mechanism (eg, painful cramps, nociceptive pain, or neuropathic pain). Given the multifactorial nature of pain in patients with ALS, different treatments have been suggested, ranging from non-steroidal anti-inflammatory drugs, drugs for neuropathic pain, opioids, and cannabinoids, to physical therapy strategies and preventive assistive devices. Further understanding of the pathophysiology is crucial to drive assessment in clinical trials of therapeutic strategies targeted at specific mechanisms and studies of individualised therapies.