A 34-year-old HIV-positive patient developed rhabdomyolysis—dangerous muscle tissue breakdown—within two weeks of starting tirzepatide (Mounjaro/Zepbound) for weight loss. Laboratory findings showed severely elevated creatine kinase levels and myoglobinuria, classic markers of muscle destruction, with symptoms resolving after drug discontinuation and aggressive hydration therapy. This represents the first documented case of tirzepatide-induced rhabdomyolysis in an HIV patient. The timing is particularly concerning given tirzepatide's explosive popularity as both a diabetes medication and weight-loss treatment, with millions of prescriptions written monthly. HIV patients already face elevated risks for muscle disorders due to their condition and antiretroviral medications, potentially creating a perfect storm when combined with GLP-1 receptor agonists. While rhabdomyolysis remains extremely rare with this drug class, this case suggests certain populations may face disproportionate risk. For clinicians, this finding underscores the need for heightened monitoring in vulnerable patients, particularly given that early symptoms—muscle pain, fatigue, dark urine—are easily dismissed as minor complaints. The case is more cautionary than paradigm-shifting but highlights gaps in our understanding of GLP-1 agonist safety profiles.