A growing body of evidence highlights the importance of the nutritional or other environmental stimuli during critical periods of development in the long-term programming of organ systems and homeostatic pathways of the organism. The adverse influences early in development and particularly during intrauterine life have been shown to programme the risks for adverse health outcomes in adult life. The mechanisms underlying developmental programming remain still unclear. However, increasing evidence has been accumulated indicating the important role of epigenetic regulation including DNA methylation, histone modifications and non-coding RNAs in the developmental programming of late-onset pathologies, including cancer, neurodegenerative diseases, and type 2 diabetes. The maternal substance abuse during pregnancy, including smoking, drinking and psychoactive drug intake, is one of the important factors determining the process of developmental programming in modern human beings. The impact of prenatal drug/substance exposure on infant and early childhood development is currently in the main focus. The long-term programming effects of such exposures on aging and associated pathologies, however, have been reported only rarely. The purpose of this review is to provide a summary of recent research findings which indicate that maternal substance abuse during pregnancy and/or neonatal period can programme not only a child's health status, but also can cause long-term or even life-long health outcomes via mechanisms of epigenetic memory.