Amyotrophic Lateral Sclerosis (ALS) is a terminal neuro-degenerative disorder of adults, typically having rapid progression and involving both motor and cognitive function. ALS exhibits considerable heterogeneity of both symptom profile and progression. Nevertheless, median survival is typically under three years from disease onset. ALS is the most common motor neurone disease in adults, with an incidence of 2 to 3 per 100,000 in Europe. The cause of ALS is unknown, however current expert opinion is that the disease occurs as a result of the combined effects of genetic and environmental factors. The primary aims of this thesis were to investigate environmental exposures as risk factors for ALS in Irish and European populations, and to investigate clinical and genetic prognostic factors in those populations. Data was obtained using the Irish ALS Register, and from Euro-MOTOR - an international, case-control study of Dutch, Irish and Italian ALS patients matched healthy controls. Overall, the findings from this thesis provide evidence that occupational and environmental exposures have importance in ALS aetiology. Spatial epidemiological analysis of the Irish ALS cohort found two significant areas of low risk for ALS, and the Euro-MOTOR study revealed associations between oral contraceptive pill use, physical activity, occupational exposures and ALS risk. These findings indicate the need for large gene-environment studies in future ALS research. Furthermore, survival analyses reinforced previous evidence that attendance at an ALS multidisciplinary clinic is associated with improved survival, and provided fresh insight into the prognostic effect of the C9orf72 expansion in ALS, indicating that stratification by C9orf72 expansion status is important in epidemiological studies. Finally, longitudinal and prognostic characteristic of subscores of the ALS Functional Rating Scale (ALSFRS) were explored and were found to be independently associated with survival. This may help to inform future clinical trial design.