Epidemiologic research is an exercise in measurement. Observational epidemiologic results usually include a point estimate, a measure of random error such as a frequentist confidence interval, and a qualitative discussion of study limitations. Without randomization of study subjects to exposure groups, inference from study results requires an educated guess about the strength of the systematic errors compared with the strength of the exposure effects. Although quantitative methods to make these educated guesses exist, the conventional approach is qualitative, which reduces the educated guessing to a problem of reasoning under uncertainty. In circumstances such as these, humans predictably reason poorly. Heuristics and resulting biases that simplify the judgmental tasks tend to underestimate the systematic error, underestimate the uncertainty, and focus the inference on the study's specific evidence while excluding countervailing external information. Common warnings to interpret results with trepidation are an ineffective solution. The methods that quantify systematic error and uncertainty challenge the analyst to specify the alternative explanations for associations that are otherwise too readily judged causal.