Bacterial infections involving muscle are quite uncommon and generally require specific predisposing factors. Bacterial myositis is more rarely described in the typical kind of patients observed in Internal Medicine (presence of multiple co-morbidities, partial/limited immune-deficiency, advanced age). Twenty-six patients suffering from bacterial myositis (8 women and 18 men; mean age 58.5 years, range 27-82) observed in a single Internal Medicine Unit were reported. Muscles involved were ileopsoas, thigh, paravertebral, gluteus, calf, forearm and rectus abdomen. Simultaneous presence of arthritis was registered in 17 patients and all patients presented relevant comorbidity. Main cultured bacteria were <em>Staphylococcus aureus, Escherichia coli</em>, other Gram-negative bacteria, <em>Streptococcus spp.</em> Multi-drug-resistance was observed in 14 out 26 (53.8%). Computed tomography, ultrasound and magnetic resonance imaging were utilized for diagnostic purposes. Antibiotic treatment was administered to all patients. Surgical debridement and drainage were performed in 12 patients; 7 patients were treated with percutaneous aspiration and drainage. At discharge, relevant functional impairment was present in 17 patients (65.3%). Four patients died (in-hospital mortality 7.6%, global mortality at three months 15.3%). Management of bacterial myositis is difficult and its prognosis is poor. In the near future, this demanding infection will be more frequently observed in Internal Medicine setting as comorbidity, which is very often the main characteristic of these patients.