With opioids being increasingly prescribed and illicit opioids being misused, substance use disorder has become a growing public health concern. The impacts of the opioid epidemic have been devastating, especially for pregnant people, infants, and children. Pre- and perinatal opioid exposure is complex. Opioids affect multiple body systems and have detrimental effects on the placenta, brain, and immune system. Pharmacological properties make each class of opioid unique, thereby compounding effects on development based on the type, receptors engaged, or combination of drugs used. Accordingly, animal models are necessary to elucidate the mechanisms, pathways, and developmental processes affected by opioid exposure during and after pregnancy. However, the complexity of opioid use in humans means that preclinical modeling is also complicated with variation by species type, duration, and timing of exposure, and combinations of opioids studied. In this chapter, we present a summary of numerous, intricate preclinical models of perinatal opioid exposure. Specifically, we discuss (1) the inherent variability and difficulty in modeling complex patterns of opioid use by pregnant and peripartum people, (2) provide background on opioids and their receptors, and (3) present evidence for long-term changes in brain structure and function secondary to prenatal opioid exposure. Together, we emphasize the significant immunological, structural, and cognitive changes documented in animals and humans after opioid exposure to highlight the potential for translatability and illustrate a path forward for improved mechanistic and therapeutic discovery.