Children living with parents who misuse substances experience multiple risk factors that at best can result in acute isolation and marginalization, and at worst lead to severe and enduring harm. This chapter explores the complexity of risk factors experienced by children and the impact of the perpetuating cycle of uncertainty and unpredictable adult behaviour. Existing literature indicates that similar risk factors associated with parental substance misuse (PSM) are also experienced by children living with other excessive parental behaviours, for example, parental problem gambling (Suomi et al., Addict Behav 126:1–12, 2022). This chapter explores the negative impact of PSM, the strain on children of carrying the burden of secrecy, experiencing multiple risk factors over a prolonged period of time and the risk to children when their emotional and physical needs are not consistently met by their parents. Importantly, this chapter also identifies protective factors in children’s lives to strengthen their resilience. While protective factors cannot erase risks, protective factors are crucial in the lives of children to act as a buffer against the harsh reality of the negative impact of PSM.