Introduction: Rheumatic disorders und their pharmacotherapy may lead to similar or even identical disorders of the central or peripheral nervous system and the skeletal muscles. It is essential to differentiate between both etiologies, since complications of the underlying rheumatic disease may require treatment escalation, whereas complications resulting from adverse effects may make it necessary to discontinue treatment and, in many cases, to start a symptomatic drug treatment. Method: Based on a literature research, this article presents the most important neurological adverse effects of the pharmacological treatment of rheumatological diseases. Results: The most severe complications are progressive multifocal leukoencephalopathy, often with a fatal outcome (azathioprine, methotrexate, cyclosporine, mycophenolate, leflunomide, tumour-necrosis factor alpha (TNF)-antagonists, rituximab), posterior reversible encephalopathy (glucocorticoids, non-steroidal antirheumatic drugs, azathioprine, methotrexate, cyclosporine, cyclophosphamide, tumour-necrosis alpha (TNF)-antagonists, rituximab), other encephalopathies (sulfasalazine, cyclosporine), optic neuropathies (cyclosporine, methotrexate, TNF-antagonists), neuropathies (dapsone, (hydroxy-) chloroquine, cyclosporine, leflunomide, TNF-antagonists), and myopathies or myositides (glucocorticoids, (hydroxy-) chloroquine, TNF-antagonists). Except for the neuropathies these complications are very rare. Further serious treatment complications are, for instance, epileptic seizures, motor and sensory disturbances. Milder complications such as headaches or tremor occur more frequently. Conclusion: New neurological signs and symptoms occurring with rheumatological pharmacotherapy may be hints for severe adverse effects. They usually require prompt neurological evaluation.