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A new theory of substance use disorders is proposed—the SPFit theory—that is based on evolutionary biology and adaptive systems. Self-perceived survival ability and reproductive fitness (SPFit) is proposed as a human psychobiological construct that prioritizes and organizes (i.e. motivates) behavior, but is highly vulnerable to temporary, artificial activation by drugs of abuse. Autoshaping/ sign-tracking/feature positive phenomena are proposed to underlie the development of craving and expectations about drugs as the individual learns that abused drugs will easily and reliably inflate SPFit. The cortico–mesolimbic dopamine system and its modulating interconnections are viewed as the biological substrate of SPFit; it is proposed to be a survival and reproductive motivation system rather than a reward center or reward pathway. Finally, the concept of modularity of mind is applied to the SPFit construct. Although considerable empirical data are consistent with the theory, new research is needed to test specific hypotheses derived from SPFit theory.