An association between consumption of cardiovascular drugs and increased risk of depression was first reported more than 30 years ago. More recently three observational studies have also reported an association between the use of cardiovascular drugs and risk of suicide. We review the epidemiological evidence with particular focus on bias, confounding, and chance as alternative explanations to a causal association. The results of the three studies are inconsistent with respect to the association between cardiovascular drug use and suicide. None of the studies has been able to control fully for possible confounding, in particular by the underlying disease and comorbidity. We thus conclude that the finding of an association between suicide risk and cardiovascular drug use remains dubious. A true explanation for the apparent increase in risk of suicide in users of cardiovascular drugs remains unknown. Future studies must try to reduce confounding. Meta-analyses of data from existing trials may be an approach to solve the problem of confounding.