Before the advent of tyrosine kinase inhibitor (TKI) therapy, the evaluation of hematologic and cytogenetic responses was sufficient to gauge treatment efficacy in patients with chronic myeloid leukemia. However, with more potent TKI therapies, the majority of patients achieve complete cytogenetic response. Furthermore, deeper molecular responses are now commonly achieved, necessitating a reliance on molecular monitoring to assess residual leukemic disease. The prognostic significance between molecular responses and duration of complete cytogenetic response, progression-free survival, and event-free survival is described herein. A discussion of the concept of complete molecular response is also provided, and the potential for imatinib treatment discontinuation is evaluated. The implications of rising BCR-ABL1 transcript levels and caveats of molecular monitoring are also described. Cancer 2011. © 2010 American Cancer Society.