Pain, agitation, delirium, and analgosedation exposure, consequences of pediatric critical illness, are associated with negative sequelae including increased mortality, length of stay, anxiety, post-traumatic stress disorder, impaired neuro-cognitive development, and reduced health-related quality of life, among others. Therapeutic cuddling is a potential intervention to address pediatric intensive care unit (PICU) pain, agitation, delirium, and analgosedation exposure. It involves physical contact such as cuddling, snuggling, or hugging, between a caregiver and child. Despite evidence of benefit in critically ill neonates and hospitalized and healthy children, there is a paucity of literature in critically ill children. The aim of this dissertation was to understand the current state of PICU pain, agitation, and sedation, and inform the development and evaluation of therapeutic cuddling as a potential intervention to address these consequences of pediatric critical illness. To achieve this, theory and methodology from implementation science, knowledge translation, and epidemiology were employed. In the first manuscript, we conducted a systematic review of the prevalence of pain, agitation, and sedation in PICUs. We found variability in measurement, conceptualization, and reporting, with prevalence estimates of 45-82% for pain, 2-42% for agitation, and 9-62% for oversedation. The second manuscript is a secondary analysis of five point-prevalence studies on early acute rehabilitation (PARK-PICU studies) aimed at describing the prevalence of therapeutic cuddling and potential safety events in PICUs from North America, South America, Europe, and Australasia. Multilevel multivariable logistic regression identified patient-level variables associated with therapeutic cuddling. The prevalence of therapeutic cuddling was 37.4%, and the prevalence of potential safety events was 2.8%. The third manuscript is a mixed methods cross-sectional survey based on the Theoretical Domains Framework administered to healthcare professionals in Canadian PICUs aimed at understanding important barriers and facilitators to therapeutic cuddling. Identified barriers included beliefs about risk and safety, staffing, and lack of prioritization of therapeutic cuddling. The most important facilitator was family participation. The results of these three manuscripts address knowledge gaps related to the prevalence of pain, agitation, and sedation and the current state of therapeutic cuddling in critically ill children. Together these provide a foundation for the development and evaluation of therapeutic cuddling as a potential intervention to address PICU pain, agitation, and analgosedation exposure.