Medical evidence is rapidly changing the way we practice oncology, especially with recent advances in targeted, combination and immunotherapies. In parallel, changes in reimbursement drive the need to deliver high-quality care as efficiently as possible. Moffitt Cancer Center’s clinical pathways (CP) are evidence-based, consensus-driven, multidisciplinary care pathways, designed to document Moffitt’s state-of-the-art best practices and reduce unnecessary variation in cancer care. In this talk, an overview of Moffitt’s CP program will be provided, including a description of the pathways themselves: 55 cancer-specific pathways, including, as appropriate, diagnostics, molecular profiling, surgery, radiation, chemotherapy, immunotherapy, clinical trials, supportive care and survivorship care. Several of Moffitt’s CP’s are integrated within the electronic medical record (EMR), facilitating decision support at the point of care. Novel reporting allows providers to track numbers of patients added to a pathway, as well as the distribution of patients across nodes of the pathway. Percentages of eligible patients treated on pathway can be estimated using a combination of data from the EMR and cancer registry. Of importance, CP’s provide a vehicle for translation of new evidence into standardized practice, through biannual reviews of CP content and ad hoc updates triggered by recent regulatory approval of novel therapies. In turn, data generated from CP’s can provide ‘real-world evidence’ of drug effectiveness in large numbers of patients who would not necessarily be eligible for clinical trials, and results from comparative effective studies can also be used to refine the content of CP’s. The value proposition of CP’s is ultimately defined by demonstration of superior patient outcomes and reduced variation in treatment costs. Advances and ongoing challenges in related CP analytics will be discussed.