Chronic pain is one of the most prevalent and costly public health concerns, and many common chronic pain conditions predominantly or uniquely impact women and girls. Significant advances in pain research have allowed for the understanding of neurobiological, inflammatory, hormonal, behavioral, and psychosocial factors that impact the pain experience of women and girls, although systemic sex biases in pain research and treatment continue to persist. These biases include the failure to fund research focusing on female-specific pain conditions, document and analyze data from female research subjects (animal and human) in research studies, and recognize the validity of women’s pain in clinical care. A holistic framework utilizing the biopsychosocial approach that focuses on individual needs and vulnerabilities is critical to effectively treating chronic pain in women and girls.