Background: Misuse of codeine-containing medicines is an emerging public health issue. Aims: We present the application of Liese and Franz's (1996) cognitive developmental model of substance abuse to the trajectory from legitimate codeine use for pain, towards that of therapeutic and other forms of misuse, and physical and psychological dependence. It illustrates a cognitive behavioural analysis of the experiences of codeine misusers - which surfaces' the specific beliefs, thoughts, emotions and behaviours of this group of hidden codeine dependent individuals, who are distinct and unique from other opioid-dependent cohorts. Method: In-depth one-to-one interviews with codeine misusers and dependent individuals in Ireland (n = 21) and South Africa (n = 25) are analysed and applied to Liese and Franz's (1996) cognitive developmental model of substance abuse. Results: Misuse and dependence pathways are maintained by the interplay between physiological determinants relating to pain, withdrawal and tolerance, and psychological influences such as therapeutic need, pre-empting of anticipated physical pain, pleasure from the dreamy sedative opiate effect of codeine and relief of emotional distress. Progression towards habitual use and misuse for therapeutic and intoxication purposes appears to be mediated by external environmental triggers pertaining to availability, internal meta-cognitions around physical pain and emotional distress, and increasing importance of codeine in the life of the user. Conclusion: The concept mapping of codeine misuse and dependence presented here could provide psychological therapists working with individuals experiencing problems with codeine, misusing codeine and those with iatrogenic dependence, with an enhanced understanding of the key concepts involved in misuse and recovery pathways.