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C an we obtain interesting and valuable knowledge from observed associations of the sort described by Greenland and colleagues 1 in their paper on risk factor epidemiology? Greenland argues "yes," and we agree. However, the really important and difficult questions are when and why. Answering these questions demands a clear understanding of the problems involved when going from observed associations of risk factors to causal hypotheses that account for them. Two main problems are that 1) thedoi:10.1097/01.ede.0000135912.17991.72 pmid:15308948 fatcat:kx2jnsmeh5da7lztnctedo4ltq