Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with no known effective treatment or cure. Clinicians often expect that ALS patients will experience depression following the diagnosis because ALS is a terminal disease. The objective of the current study was to examine the evidence from the literature on psychological health in ALS patients in order to determine the prevalence and severity of depression in this population. Twenty-eight studies of ALS patients, conducted over the past 20 years, were reviewed and evaluated. The cumulative evidence suggests that clinically significant depression is neither as prevalent nor as severe as might be expected. Methodological limitations that are inherent to the measurement of depression in ALS, including the lack of appropriate instruments, small sample sizes, and reliance on cross-sectional data, have contributed to the wide range of reported results. We conclude that ALS patients are more likely to present with hopelessness and end-of-life concerns than clinically significant depression. It is important to assess a broad range of potential psychological distress early in the course of ALS, rather than focus specifically on depression, because the manner in which patients cope with their disease can affect their longevity.