Important advances in the understanding of the molecular basis of chronic myeloid leukemia have resulted in the development of new therapies and changed the paradigm for managing this myeloproliferative disease. Translocation of chromosomes 9 and 22 (known as the Philadelphia chromosome) results in a fusion BCR-ABL gene that produces a dysregulated BCR-ABL tyrosine kinase protein and triggers events leading to malignant transformation. The tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib block the BCR-ABL protein and prevent activation of the transformation pathways. Molecular monitoring, the most sensitive approach currently available to assess treatment response, measures BCR-ABL messenger RNA levels and serves as a surrogate marker of disease. Further, molecular responses are predictive of patient outcomes. It is important for advanced practitioners to become familiar with the technology and interpretation of molecular monitoring results as well as efforts to standardize this type of testing so they can educate their patients and aid their understanding of test results. Undetectable BCR-ABL levels can bring feelings of relief, whereas an increasing level can lead to anxiety. Advanced practitioners, therefore, are an important resource for interpreting results for patients, answering questions, alleviating concerns, and encouraging continued adherence to treatment.