Two research areas that could benefit from a greater focus on the role of the reward pathway are maternal depression and maternal addiction. Both depression and addiction in mothers are mediated by deficiencies in the reward pathway and represent substantial risks to the health of offspring and future generations. This targeted review discusses maternal reward deficits in depressed and addicted mothers, neural, genetic, and epigenetic mechanisms, and the transgenerational transmission of these deficits from mother to offspring. Postpartum depression and drug use disorders may entail alterations in the reward pathway, particularly in striatal and prefrontal areas, which may affect maternal attachment to offspring and heighten the risk of transgenerational effects on the oxytocin and dopamine systems. Alterations may involve neural circuitry changes, genetic factors that impact monoaminergic neurotransmission, as well as growth factors such as BDNF and stress-associated signaling in the brain. Improved maternal reward-based preventative measures and treatments may be specifically effective for mothers and their offspring suffering from depression and/or addiction.