Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential.