Intractable hiccups are a relatively uncommon condition characterized by involuntary, spasmodic contractions of the diaphragm. This type of hiccups generally has a duration of more than 1 month. We describe a 59-year-old kidney transplant recipient with a complicated medical history (atrial fibrillation, chronic renal failure, type 2 diabetes mellitus, gastroesophageal reflux, gout, hypertension, hyperlipidemia, and obstructive sleep apnea) who developed intractable hiccups that significantly affected his quality of life. Despite an extensive gastrointestinal and pulmonary evaluation, and treatment failures with several different drug regimens—metoclopramide, desipramine, amantadine, cyclobenzaprine, phenytoin, and lorazepam—his hiccups were eventually controlled with a combination of baclofen and low-dose olanzapine therapy. Baclofen is a γ-aminobutyric acid (GABA) analog that contains a phenylethylamine moiety. It is hypothesized that having both GABA and phenylethylamine properties activates inhibitory neurotransmitters, most notably GABA, which may in turn block the hiccup stimulus. The exact mechanism through which olanzapine is effective in patients with hiccups is not fully understood. It is thought that the effect is, in part, due to serotonin augmenting phrenic motoneuronal activity on the reflex arcs involved in the generation of hiccups within the spinal cord. In addition, since olanazapine is a dopamine antagonist, particularly a dopamine D2-receptor antagonist, this could also have played a role in its effectiveness in treating our patient. Strong evidence for a specific treatment regimen for intractable hiccups is lacking in the primary literature. Our case report adds to the available literature, as there are currently no published data on the use of combination therapy for the treatment of intractable hiccups, and the combination of baclofen and olanzapine significantly improved our patient's quality of life.