In the past few years, international treatment guidelines for chronic myeloid leukaemia have incorporated recommendations for attempting discontinuation of treatment with tyrosine-kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of a treatment-free remission (TFR). Physicians involved in the treatment of chronic myeloid leukaemia need to be sufficiently well informed to guide patients through decision-making about the discontinuation of treatment with TKIs targeting BCR-ABL1 by providing a balanced assessment of the potential risks and benefits of stopping or continuing therapy. These guidelines also seek to ensure that the risks associated with being off treatment are kept to a minimum. In this Review, we summarize the clinical studies of TFR and how their results can guide routine clinical practice with a focus on specific aspects such as molecular monitoring and the pregnancy-specific risks associated with a TFR attempt in female patients. We also address the development of predictors of outcome after TKI discontinuation and present strategies that warrant further consideration to enable more patients to enter TFR.