Rhabdomyolysis (CK >10 times upper limit of normal, with evidence of renal injury) is exceed- ingly rare and usually encountered in the setting of a patient with several predisposing comorbidities and concomitant high-risk medications.S5-1,S5-22,S5-30 It requires immediate medical attention. 3. Before lipid-lowering therapy with a statin is initiated, a comprehensive evaluation of mus- culoskeletalsymptoms(withdocumentation)isrec- ommended because such symptoms are common at baseline in the general adult population.S5-3 S5-6 Beforetherapy,itisalsoimportanttoidentifypredis- posing factors for SAMS, including demographics, comorbid conditions, and use of medications that can adversely affect statin metabolismS5-3,S5-13,S5-14 (Table 11). Proactive and preemptive identification of patients at potential increased risk of statin- associated side effects should help guide informed clinical decision-making and is supportive of the goals of safe and effective therapy. 4. Several creatively designed randomized crossover trials in patients with SAMSS5-3 S5-7 support a man- agement strategy of statin discontinuation until symptoms improve, followed by rechallenge with a reduced dose, alternative agent, or alternative dosing regimen while monitoring for recurrent symptoms. If the approach of reassess, rediscuss (net clinical benefit), and rechallenge is used, a majority of patients will be able to be successfully treated with at least one or several statins.S5-29,S5-31 In patients at increased ASCVD risk, the goal should be to treat with the guideline-recommended max- imally tolerated statin dose. Patients who experi- ence rhabdomyolysis with statin therapy may need to discontinue statin use indefinitely, although reversible causes should be sought.S5-32 Clinicians should be aware of a rare disorder, statin-associ- ated autoimmune myopathy (muscle weakness, marked and persistent CK elevation, presence of HMG CoA reductase [HMGCR] antibodies, necrotizing myopathy, and lack of or incomplete resolution on statin discontinuation), that requires statin cessation and additional therapy directed at the autoimmune process.S5-32 Patients with statin- associated autoimmune myopathy may benefit from seeing a neurologist specializing in neuro- muscular disorders. 