Women with substance use problems face a number of gender-specific challenges that affect key aspects of assessment and treatment. From the outset, the initial trajectory that leads a woman to develop a substance misuse problem involves higher rates of childhood maltreatment that in turn can have a profound effect on adult wellbeing. The use of illicit substances typically requires access to large sums of money and to drug dealers. Many women manage this by an association with a drug-using partner and/or involvement in sex work. This results in a complex interplay between drug supply and violence and victimisation. Added to this difficult picture are concerns around parenting in a high-risk context and the additional shame and stigma that deter women from seeking treatment. Primary care practitioners are well positioned to help women with substance misuse problems in the course of routine clinical care. Such opportunities typically present around contraception, pregnancy and child health issues. It is possible to identify women with substance use problems by asking a series of simple questions that may provide an opportunity for engagement in either treatment with the primary care practitioner and/or liaison with specialist agencies. This chapter will provide an overview of the key gender differences with a focus on prevalence, treatment engagement, physical and psychological sequelae of substance use and, finally, the special issues around management of pregnant women and their babies in the immediate postpartum period. A focus on parenting of young infants, outcomes for children raised in families with parental substance misuse and safeguarding concerns are discussed in this chapter.