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The success of high-dose buprenorphine (HDB) as substitution therapy for major opioid dependence is related to its partial agonist effect on opioid receptors, which in theory makes it very safe to use. However, numerous deaths directly attributable to buprenorphine have been described in the literature. These deaths are generally related to misuse of HDB with intravenous administration and/or concomitant use of benzodiazepines, and they usually occur in patients on HDB substitution therapy for opioid dependence. We present three deaths attributed to HDB which arose from uncommon mechanisms and led to unusual forensic situations. The first death was that of a patient admitted to hospital after simultaneous prescription of HDB, clonazepam, oxazepam, and cyamemazine. The second death followed forcible administration of a very low dose of HDB to a patient with post-hepatitis C cirrhosis and heart failure. The third death was subsequent to an HDB overdose, probably with suicidal intent, in a young woman who had not been prescribed the drug as opiate substitute. Such deaths raise the question of the mechanisms involved and draw attention to the resulting unusual forensic situations.