Motor neuron diseases (MNDs) are a group of devastating neurologic disorders that cause specific damage to the motor neuron cells. The current diagnosis of MND is based on results of the clinical examination and neurophysiologic studies. The length of time of referral to a neuromuscular neurologist and the lack of validated diagnostic criteria can delay diagnosis. Although the role of imaging is currently most useful in excluding other conditions, several attempts to incorporate neuroimaging in the diagnosis of the disease and assessment of progression have shown promising results.We conducted a literature review via searches in PubMed and The Cochrane Database using multiple relevant terms to the topic. Two cases with a challenging diagnosis of MND are described, with a thorough discussion of how the diagnosis was suggested on the basis of magnetic resonance imaging evidence in each case. Advanced magnetic resonance imaging findings can be useful tools that add to the diagnostic criteria of MNDs, especially in cases where reaching a definitive diagnosis is difficult. Such findings might enable clinicians to reach an early diagnosis that can improve the patient's quality of life and prolong survival.