Background: The aim of this study was (1) to apply the current United Kingdom (UK) National Institute for Health and Care Excellence (NICE) clinical practice guidelines to a hypothetical older patient with multimorbidity and life-limiting illness; (2) consider how treatment choices could be influenced by NICE guidance specifically related to multimorbidity; and, (3) ascertain if such clinical practice guidelines describe how and when medication should be reviewed, reduced and stopped. Methods: Based upon common long-term conditions in older people, a hypothetical older patient was constructed. Relevant NICE guidelines were applied to the hypothetical patient to determine what medication should be initiated in three treatment models: a new patient model, a treatment-resistant model, and a last-line model. Medication complexity for each model was assessed according to the medication regimen complexity index (MRCI). Results: The majority of the guidelines recommended the initiation of medication in the hypothetical patient; if the initial treatment approach was unsuccessful, each guideline advocated the use of more medication, with the regimen becoming increasingly complex. In the new patient model, 4 separate medications (9 dosage units) would be initiated per day; for the treatment-resistant model, 6 separate medications (15 dosage units); and, for the last-line model, 11 separate medications (20 dosage units). None of the guidelines used for the hypothetical patient discussed approaches to stopping medication. Conclusions: In a UK context, disease-specific clinical practice guidelines routinely advocate the initiation of medication to manage long-term conditions, with medication regimens becoming increasingly complex through the different steps of care. There is often a lack of information regarding specific treatment recommendations for older people with life-limiting illness and multimorbidity. While guidelines frequently explain how and when a medication should be initiated, there is often no information concerning when and how the medications should be reduced or stopped.