ABSTRACT Hypokalemic periodic paralysis is a hereditary or acquired temporary flaccid paralysis of skeletal muscles, affecting proximal musculature more than distal, as a result of hypokalemia. In this report, we describe a unique case of amphetamine‐induced hypokalemic periodic paralysis that has only been described twice in the current literature. A 31‐year‐old male with a history of substance abuse presented with altered mental status and acute tetraparesis after inhalation of methamphetamine. Labs were significant for marked hypokalemia (1.8 mmol/L), elevated creatine kinase and a positive urine drug screen for methamphetamines. Aggressive potassium replacement was initiated, yet the patient remained hypokalemic, with worsening neurological status and aphasia. Intubation and mechanical ventilation became a necessity after the patient developed acute hypercapnic respiratory failure (pCO 2 103 mmHg, pH 7.02). Our patient then received potassium replacement via multiple routes, including intravenous and orogastric administration. After 15 h, his potassium normalised, and he was successfully extubated the next day, regaining full motor strength. This case highlights the potential for amphetamine‐induced hypokalemic periodic paralysis to cause life‐threatening diaphragmatic paralysis and respiratory failure. How methamphetamine exactly induces hypokalemic periodic paralysis remains unclear, yet its indirect sympathomimetic effects with subsequent intracellular potassium shifts possibly explain the resultant hypokalemia. Given that methamphetamine use is on the rise, physicians should have a high index of suspicion for amphetamine‐induced hypokalemic periodic paralysis in patients presenting with acute paralysis and a substance use history. Rapid recognition, potassium repletion and respiratory monitoring are essential for patient recovery.